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ID PMID Title PublicationDate abstract
11996158 Oral findings in patients with primary Sjögren's syndrome and oral lichen planus--a preli 2002 Mar Bovine colostrum is rich in antimicrobial substances and growth factors. The purpose of this open study was to examine and compare the interventory effects of daily use of bovine colostrum-containing oral hygiene products (CHP) on oral symptoms and findings in 20 patients with primary Sjogren's syndrome (pSS) and 20 age-matched patients with oral lichen planus (OLP). Objective oral measures and self-assessment of oral symptoms and general health were conducted before and after 90 days' use of CHP. The pSS patients had more systemic diseases, medication intake, oral dryness, poorer general health and lower salivary secretion than the OLP patients, who had the highest plaque index (PI) and the most mucosal soreness. Oral dryness and soreness were correlated to general health. In both patient groups. unstimulated whole saliva flow rate (UWS) had increased, PI and periodontal pocket depth (PPD) were reduced, and general health and oral dryness and soreness had improved after using CHP. A decrease in hyphae was found in candida smears from both groups and in blastospores in OLP smears. A reduction in the extension of the mucosal lesions was observed in 15 OLP patients. Results suggested beneficial effects of intervention with CHP on oral symptoms, general health, UWS, PI, PPD and candidal load in two patient groups--pSS and OLP--representing different oral symptomatology.
15848146 P2Y2 nucleotide receptor up-regulation in submandibular gland cells from the NOD.B10 mouse 2005 Jun Sjögren's syndrome (SS) is an autoimmune disease that specifically targets exocrine glands, including salivary glands, and results in an impairment of secretory function. P2Y(2) nucleotide receptors for extracellular ATP and UTP are up-regulated in response to stress or injury in a variety of tissues including submandibular glands (SMGs) [Ahn JS, Camden JM, Schrader AM, Redman RS, Turner JT. Reversible regulation of P2Y(2) nucleotide receptor expression in the duct-ligated rat submandibular gland. Am J Physiol Cell Physiol 2000;279:C286-94; Hou M, Malmsjö M, Möller S, Pantev E, Bergdahl A, Zhai X-H, et al. Increase in cardiac P2X(1)- and P2Y(2)-receptor mRNA levels in congestive heart failure. Life Sci 1999;65:1195-206; Kishore BK, Wang Z, Rab H, Haq M, Soleimani M. Upregulation of P2Y(2) purinoceptor during ischemic reperfusion injury (IRI): possible relevance to diuresis of IRI. J Am Soc Nephrol 1998;9:581 (abstract); Koshiba M, Apasov S, Sverdlov V, Chen P, Erb L, Turner JT, et al. Transient up-regulation of P2Y(2) nucleotide receptor mRNA expression is an immediate early gene response in activated thymocytes. Proc Natl Acad Sci U S A 1997;94:831-6; Turner JT, Landon LA, Gibbons SJ, Talamo BR. Salivary gland P2 nucleotide receptors. Crit Rev Oral Biol Med 1999;10:210-24; Seye CI, Gadeau AP, Daret D, Dupuch F, Alzieu P, Capron L, et al. Overexpression of the P2Y(2) purinoceptor in intimal lesions of the rat aorta. Arterioscler Thromb Vasc Biol 1997;17:3602-10; Seye C, Kong Q, Erb L, Garrad RC, Krugh B, Wang M, et al. Functional P2Y(2) nucleotide receptors mediate uridine 5'-triphosphate-induced intimal hyperplasia in collared rabbit carotid arteries. Circulation 2002;106:2720-6]. OBJECTIVE: To assess whether P2Y(2) receptor expression is up-regulated in SMGs of the NOD.B10 mouse model of primary SS as compared to SMGs of normal C57BL/6 mice. DESIGN: SMG cells were isolated from normal C57BL/6 and diseased NOD.B10 mice. P2Y(2) receptor mRNA expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization, whereas functional P2Y(2) receptor activity was analyzed by measuring UTP-induced increases in [Ca(2+)](i). RESULTS: In contrast to SMG cells from C57BL/6 mice, SMG cells from 4- to 19-week-old NOD.B10 mice exhibited increased P2Y(2) receptor mRNA localized to both ductal and acinar cell types. The levels of mRNA for other uridine nucleotide receptors, i.e., P2Y(4) and P2Y(6) receptors, showed no significant differences between SMG cells of C57BL/6 and NOD.B10 mice, suggesting that only the P2Y(2) receptor was up-regulated in NOD.B10 mice. Moreover, P2Y(2) receptor activity in SMG cells from NOD.B10 mice increased with age (i.e., disease progression). CONCLUSION: P2Y(2) receptor up-regulation in SMGs is associated with the SS phenotype in NOD.B10 mice, which encourages further attempts to determine the role of this pathway in the development of SS.
12928945 [Spontaneous achilles tendon rupture in granulomatous vasculitis]. 2003 Aug A 66-year old patient sustained a non-traumatic rupture of her left achilles tendon. She suffered from Sjögren's syndrome which occurred in conjunction with a systemic vasculitis, and recurrent episcleritis. The combination of Sjögren's syndrome and systemic vasculitis is well known. Subsequently, she was treated with high-dose systemic steroids over a period of 2 years. In order to reduce the amount of steroids due to preexisting severe osteoporosis and thoracic vertebral fractures, her medication was changed to cyclophosphamide shortly before her injury. Intraoperatively, a granuloma was discovered at the site of the rupture. This granuloma had infiltrated most of the achilles tendon at this site and virtually replaced viable tendon tissue. Originally, the rupture was supposedly due to the high dose steroids. This theory had to be revised according to the intraoperative findings. Following excision of the granuloma and operative treatment of the achilles tendon rupture, the continuity of the tendon could be completely restored. A MRI scan 3 months after the procedure demonstrated a completely healed Achilles tendon. Spontaneous achilles tendon rupture due to a granuloma in patients with vasculitis seems to be a rare event. However, tendon ruptures in combination with systemic lupus erythematodes have been described. Mostly, these events are attributed to long term application of steroids. Spontaneous rupture in combination with high dose treatment of steroids seems to be an underestimated problem.
12389174 [Retrovirus, mycotoxins, immunosuppression and neurodegeneration]. 2002 Sep 16 AIMS: To analyse the pros and cons of the etiopathogenic aspects of the different clinical entities that, over the years, have been found to be associated with the so called human retroviruses in order to propose possible etiological alternatives. METHOD: Since research on retroviruses began there has been a tendency to blame these elements for a number of clinical entities, the most important of which include Aids, tropical spastic paraparesis (TSP), fungoid mycosis, Sjogren's syndrome and T cell leukaemia. Yet many patients and scientific publications point out the existence of a large number of clinical and laboratory inconsistencies, which suggests that the so called cofactors associated with all these entities are far more likely to be the real generators of these public health problems. Among these, we pay special attention to environmental toxins, of which a prototypical example is the group of neuromycotoxins. There are several ways these can enter the organism of an individual exposed to them (through food, breathing and intravenously) or, worse still, they can be generated endogenously in immunosuppressed individuals. CONCLUSION: The possibility of some cofactors being the real causes behind a large number of entities considered to be Aids, TSP, Sjogren s syndrome, fungoid mycosis or T cell leukaemia, among others, regardless of their retroviral serological state, is becoming more and more likely and scientifically plausible. All these facts should be researched in much greater depth to determine their real dimensions, which would therefore enable us to face the future with better means of prevention, diagnosis and treatment at our disposal.
11967114 Expression of the B cell-attracting chemokine CXCL13 in the target organ and autoantibody 2002 Apr Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltrates resembling secondary lymphoid organs in salivary glands. In this study, we demonstrate the expression of the lymphoid tissue homing chemokine CXCL13 (BCA-1/BLC), which has attracting properties for B cells and subsets of activated T cells, in salivary glands of patients with Sjögren's syndrome using immunohistochemistry and in situ hybridization. CXCL13 expression was primarily observed in epithelial cells in acini and ducts of inflamed glands while its receptor, CXCR5 (BLR-1), was expressed on the infiltrating mononuclear cells. In addition, cells producing antibodies against one of the major autoantigens in Sjögren's syndrome, Ro 52, were identified at the periphery of the follicular infiltrates indicating that the ectopic lymphoid tissue is directly involved in the disease process. Identification of CXCL13 and CXCR5 in salivary glands suggests that the target organ plays an essential role in the inflammatory process by recruiting B and T cells. These results also provide a molecular mechanism by which lymphoid neogenesis and ectopic germinal centre formation might occur in the glands of these patients, which may be the key step in the development of the chronic inflammatory process in Sjögren's syndrome.
11871764 Primary hepatic lymphoma in a patient with Sjögren's syndrome. 2002 We report a case of primary hepatic lymphoma (PHL) that developed in a patient with well controlled Sjogren's syndrome (SS) who had been receiving long-term prednisolone treatment. The tumor, found incidentally by ultrasonography, was shown as an extremely large, solitary liver mass that exhibited the immunohistological features of a B-cell lymphoma. An intensive regimen of chemotherapy induced complete regression of this mass. SS occasionally gives rise to lymphoma in salivary glands, however, there have been no previous reports of PHL in a patient with SS. This case study raises the possibility that SS itself, a form of autoimmune disease, and/or prednisolone-based immunosuppressive treatment for SS, predisposes to the occurrence of PHL. SS patients should be monitored vigilantly for the occurrence of extranodal lymphoma, including PHL, even if the SS is well controlled.
15561677 Congenital and acquired neutropenia. 2004 Our understanding of the pathogenesis of congenital and acquired neutropenia is rapidly evolving. New ground-breaking observations have identified the genes responsible for many of the congenital neutropenia syndromes and are also providing new insights into normal neutrophil commitment and differentiation. Acquired neutropenia remains a poorly understood syndrome, although new insights into its pathogenesis are also emerging, especially with regard to subsets of immune neutropenia. In Section I, Dr. Marshall Horwitz reviews the current understanding of the genetic basis, molecular pathology, and approaches to treatment of congenital neutropenia and cyclic hematopoiesis. Mutations in the ELA2 gene, which encodes for neutrophil elastase, cause cyclic hematopoiesis. ELA2 mutations are also the most common cause of congenital neutropenia, where their presence may equate with a more severe clinical course and higher frequency of leukemic progression. Emerging evidence indicates interrelatedness with Hermansky Pudlak syndrome and other disorders of neutrophil and platelet granules. In Section II, Dr. Nancy Berliner presents an overview of the clinical approach to the evaluation and treatment of acquired neutropenia. This includes a review of the pathogenesis of primary and secondary immune neutropenia, drug-induced neutropenia, and non-immune chronic idiopathic neutropenia of adults. Studies used to evaluate patients for potential immune neutropenia are reviewed. Management issues, especially the use of granulocyte colony-stimulating factor (G-CSF), are discussed. In Section III, Dr. Thomas Loughran, Jr., reviews the pathogenesis and clinical manifestations of large granular lymphocyte (LGL) leukemia. Possible mechanisms of neutropenia are discussed. In particular, discussion focuses on the relationship between LGL leukemia, rheumatoid disease, and Felty's syndrome, and the complex interplay of defects in neutrophil production, distribution, destruction, and apoptosis that underly the development of neutropenia in those syndromes.
14760793 Autoimmune response to proteasome activator 28alpha in patients with connective tissue dis 2004 Feb OBJECTIVE: To determine the autoimmune response against proteasome activator 28alpha (PA28alpha) in patients with various connective tissue diseases, and to compare the immunoreactivity between anti-PA28alpha and anti-Ki antibodies. METHODS: Serum samples were obtained from 219 patients with various connective tissue diseases. cDNA encoding full-length human PA28alpha and Ki were produced by polymerase chain reaction. Antigens were expressed as glutathione S-transferase (GST) fusion proteins. The immunoreactivity of serum for PA28alpha and Ki was studied by Western blotting. An inhibition test was performed by ELISA using purified Ki antigen. RESULTS: Anti-PA28alpha> antibody was detected in serum from 23% of patients with systemic lupus erythematosus (SLE) and 24% with Sjögren's syndrome (SS). These rates were significantly higher than those for the other rheumatic diseases. Since both PA28alpha and Ki are elements of the PA28 complex and their amino acid sequences share 40.2% homology, immunoreactivity to PA28alpha was studied further. Among 27 anti-Ki positive serum samples, 13 samples (48%) also reacted with PA28alpha, suggesting a relationship between anti-PA28alpha and anti-Ki antibodies. To investigate whether this finding was due to the presence of cross-reacting epitopes for PA28alpha and Ki antigens, an inhibition test was performed by ELISA. The reactivity to purified Ki antigen was not inhibited by preincubation with recombinant PA28alpha. CONCLUSION: Detection of anti-PA28alpha antibody was significantly higher in serum from patients with SLE and SS. The relationship between anti-PA28alpha and Ki antibodies suggests the importance of an antigen-driven system in the induction of an autoimmune response to PA28 complex.
14650168 [Abnormal interferon-inducible protein-10 expression in the labial glands of patients with 2003 Oct OBJECTIVE: To investigate whether interferon-inducible protein 10 (IP-10) is involved in the inflammatory process of the labial gland of patients with Sjogren's Syndrome (SS). METHODS: Forty-nine patients performed labial gland biopsy, the number of lymphocytes in the biopsy tissues was calculated and the IP-10 was detected by the methods as following: 39 biopsied labial tissues were examined by RT-PCR, among them, 21 were from primary SS, 5 from secondary SS and 13 from other diseases. With RT-PCR, the IP-10 and beta-actin were co-amplified with specific primers. The gel-fractioned and ethidium bromide amplification products were then analyzed by densitometry. The expression of IP-10 was semi-quantificated by IP-10/beta-actin ratio. Twenty-one samples were examined by immunohistochemistry with specific goat anti-IP-10 antibody, 10 of them from primary SS, 3 from secondary SS, 8 from other diseases. 11 out of 21 samples were examined by both RT-PCR and immunohistochemistry. RESULTS: The expression of IP-10 mRNA was significantly up-regulated in labial glands of patients with SS compared with other diseases (IP-10/beta-actin ratio was 0.329 +/- 0.157 vs 0.099 +/- 0.059, P < 0.01). The number of lymphocyte infiltration foci in labial glands of patients with SS correlated to the IP-10/beta-actin ratio (r = 0.657, P < 0.05). Ductal epithelial cells and some of the infiltrating lymphocytes were stained by anti-IP-10 antibody by immunohistochemistry in 8 of the primary SS (8/10), all of the secondary SS (3/3) and one with primary biliary sclerosis (1/8). The expression of IP-10 protein detected by immunohistochemistry was consistent with that of mRNA detected by RT-PCR. CONCLUSIONS: IP-10 is abnormally highly expressed in the labial glands of patients with SS and positively relates to the lymphocyte infiltration. It thus suggests chemokine IP-10 may be one of the important molecules attracting the lymphocytes to the minor salivary glands to form the lymphocytic foci of Sjogren's Syndrome.
15467582 Prospective echocardiographic evaluation of atrioventricular conduction in fetuses with ma 2004 Sep OBJECTIVE: Fetal complete atrioventricular block (AVB) occurs in 2-5% of Sjögren's antibodies (SSA/SSB)-positive pregnancies with substantial morbidity and mortality. We evaluated the incidence of 1 degrees and 2 degrees AVB by measuring Doppler-derived mechanical PR intervals. STUDY DESIGN: We compared mechanical PR intervals of fetuses of SSA/SSB positive mothers referred to a single cardiology center between 1997 and 2003 with control fetuses and fetuses with 1 degrees or 2 degrees AVB confirmed by magnetocardiography or postnatal electrocardiogram. RESULTS: One hundred thirty-nine fetal echocardiograms performed on 59 SSA/SSB-positive pregnant women at 24.3 +/- 5.0 weeks gestation were compared with 150 controls. Mechanical PR intervals of the study group (120.5 +/- 9.8 milliseconds) and controls (120.6 +/- 8.7 milliseconds) were the same but differed significantly from fetuses with 1 degrees and 2 degrees AVB (191.5 +/- 29.6 msec). CONCLUSION: The incidence of 1 degrees and degrees 2 fetal AVB in SSA/SSB-positive pregnancies is low and can be identified by abnormal mechanical PR interval.
14644864 Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis. 2003 Dec BACKGROUND: Peripheral neuropathy is a prominent feature of the systemic and secondary vasculitides. Usually, it is responsive to corticosteroids, but in certain cases it may be resistant to corticosteroid or immunosuppressive treatment, or both. OBJECTIVE: To present patients who exhibited various inflammatory diseases accompanied with vasculitic peripheral neuropathies for which intravenous immunoglobulin (IVIg) was used for treatment. METHODS: Six patients with Sjögren's syndrome, systemic lupus erythematosus (SLE), vaccination induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated with hepatitis C infection, or sarcoidosis were included. All developed vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg body weight). The patients were followed up for 1-5 years after this treatment. RESULTS: In four patients (Sjögren's syndrome, Churg-Strauss vasculitis, SLE, and vaccination induced vasculitis) the neuropathy resolved after IVIg treatment. CONCLUSION: IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment for patients with contraindications to conventional treatment, or alternatively, for patients in whom conventional treatment has failed.
12777089 Paraneoplastic antineuronal antibodies in patients with systemic autoimmune diseases. 2003 May Sera from 71 patients with primary Sjögren's syndrome (PSS) and from 102 patients with systemic lupus erythematosus (SLE) were tested by immuno-dot blotting against HuD, Ri, Yo and amphiphysin recombinant proteins. For Ri, Yo and amphiphysin antigens, no immunoreactivity was found in the 173 sera tested. One PSS patient with a clinical picture of subacute sensory neuronopathy had high titers of anti-Hu antibodies. An extensive search for an underlying tumor was initially negative but a small cell lung cancer was eventually discovered three years later. Another patient with SLE and a clinical picture of demyelinating polyradiculoneuropathy had anti-Hu antibodies. Repeated search for an underlying tumor remains negative after five years follow-up in this young non-smoking patient. In addition, the neuropathy progressively improved and the anti-Hu antibodies titer slowly decreased from 1:8000 to 1:2000, making the diagnosis of paraneoplastic syndrome unlikely in this patient. This study indicates that the detection of anti-Hu antibodies in patients with known symptomatic systemic autoimmune diseases such as PSS or SLE should induce the same work-up than the detection of these antibodies in the absence of other immune diseases, i.e. repeated search for occult cancer during several years. As illustrated by our first patient, this strategy may be fruitful. Nevertheless, the clinician should know that anti-Hu antibodies may exceptionally (0.6% in this series) occur in systemic autoimmune disorders with neurological complications, in the absence of an underlying neoplastic disease.
11923240 Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjögren syndro 2002 Apr PURPOSE: To determine whether the relative amounts of mucin mRNA in the conjunctival epithelium and mucin protein in the tears are altered in patients with Sjögren syndrome compared with healthy individuals. METHODS: Tear fluid was collected from the inferior fornix of normal subjects (n = 17) and patients with Sjögren syndrome (n = 11) after instillation of 60 microL sterile water onto the ocular surface. Immediately after tear fluid collection, conjunctival epithelium was obtained by filter paper-stripping from the bulbar temporal region for mRNA isolation. Primers to nontandem repeat sequences of the gel-forming mucin MUC5AC and the membrane-spanning mucins MUC1 and MUC4 were used in real-time RT-PCR to determine relative abundance of MUC mRNA in patients with Sjögren syndrome in relation to that of normal subjects. Enzyme-linked immunosorbent assay was performed on neuraminidase-treated tears, using a polyclonal antibody against a synthetic peptide mimicking the deduced amino acid sequence from the D3 region of MUC5AC. RESULTS: The number of RNA transcripts for the goblet cell-specific mucin MUC5AC in the conjunctival epithelium of patients with Sjögren syndrome was significantly lower than in normal individuals. No significant changes were detected when analyzing the mRNA levels of the mucins expressed by the stratified epithelium of the conjunctiva, MUC1 and MUC4. Protein levels of the goblet cell mucin MUC5AC were significantly reduced in the tear fluid of patients with Sjögren syndrome, corroborating mRNA data obtained using real-time RT-PCR. CONCLUSIONS: The tear fluid of patients with Sjögren syndrome has reduced levels of the goblet cell-specific mucin MUC5AC, which correlates to decreased levels of conjunctival MUC5AC mRNA. The authors propose that deficiency of MUC5AC mucin in tears constitutes one of the mechanisms responsible for tear film instability in Sjögren syndrome.
17679856 Alloplasty of the humeral joint. 2003 Feb 28 Background. Since 1980's, shoulder arthroplasty has become more oftenly performed procedure, and for severe comminuted fractures of proximal humerus (fou r- fragmented fractures, according to Neer's classification) has become first - line therapeutic option. At the beginnig of 90's, contemporary prinicples of shoulder arthroplasty were introduced. It is assumed that 4 mechanical parameters, i.e. range of motion, joint stability, strengh and smoothness of prosthesis components contribute to shoulder function, and we sholud reach toward their reconstruction during surgical procedure. Material and Methods. In our Department from 1995 to1999 we performed 14 shoulder hemiarthroplasties using Bio-Modular prosthesis (12 women and 2 men). Patients' age ranged from 41 to 75 years (average 61.8 years). Indications included: acute comminuted proximal humerus fractures, proximal humerus malunions, and either degenerative arthritis or rheumatoid arthrits of the shoulder. Aftertreatment consisted of passive motions introduced on the first day after an operation, followed by assisted active excercises 4- 6 weeks later, and motions against resistance, allowed 2 months postoperatively. Results. The outcomes were evaluated three years after surgery, and were measured as the score in the Constant scale and as subjective patients' assesments. Improvement was seen as an increase from average 28.3 preoperative Constant score, to 60.3 postoperatively. Subjectively, excellent outcome was reported by 4 patients, good - by 7, and fair by 2 patients. Conclusions. Our experience shows that whereas indications to shoulder artrhroplasty are not frequent in cases of fractures or orthopedic conditions of the affected region, in properly selected group of patients this procedure is effective treatment option, alleviating pain and allowing for regaining well - functioning joint, but long-lasting, at leats one-year long rehabilitation programm after surgery is mandatory.
12005339 Results of Sauve-kapandji procedure. 2002 Mar INTRODUCTION: Sauve-Kapandji procedure is used to treat distal radioulnar joint disorder. MATERIALS AND METHOD: Sixteen patients with distal radioulnar joint (DRUJ) disease treated with Sauve-Kapandji procedure between 1996 and 1998 were available for review at an average follow up period of 32.8 months,ranging from 24 to 48 months. The patients were young and the average age at the time of procedure was 33.6 years. There were eight cases of post-traumatic DRUJ arthritis, two cases of dislocation of DRUJ with malunion of radial fractures and six cases of rheumatoid patients with destruction of DRUJ. The distal end of ulnar shaft was stabilised with a sling created using radial 1/2 slip of extensor carpi ulnaris (ECU) tendon. Functional results were evaluated with Mayo wrist score. RESULTS: Fusion of DRUJ was achieved in all cases by two months. Excellent results were achieved in eight cases, good in six, fair in one and poor in one. All except one case gained increase range of forearm rotation. Complications included one case of closure of pseudoarthrosis and required excision of the ulna head to restore forearm rotation. CONCLUSION: Sauve-Kapandji procedure is recommended in young patients with distal radioulnar joint disorder.
12165536 Annexin 1 modulates monocyte-endothelial cell interaction in vitro and cell migration in v 2002 Aug 15 The effect of the glucocorticoid inducible protein annexin 1 (ANXA1) on the process of monocytic cell migration was studied using transfected U937 cells expressing variable protein levels. An antisense (AS) (36.4AS; approximately 50% less ANXA1) and a sense (S) clone (15S; overexpressing the bioactive 24-kDa fragment) together with the empty plasmid CMV clone were obtained and compared with wild-type U937 cells in various models of cell migration in vitro and in vivo. 15S-transfected U937 cells displayed a reduced (50%) degree of trans-endothelial migration in response to stromal cell-derived factor-1alpha (CXC chemokine ligand 12 (CXCL12)). In addition, the inhibitory role of endogenous ANXA1 on U937 cell migration in vitro was confirmed by the potentiating effect of a neutralizing anti-ANXA1 serum. Importantly, overexpression of ANXA1 in clone 15S inhibited the extent of cell migration into rheumatoid synovial grafts transplanted into SCID mice. ANXA1 inhibitory effects were not due to modifications in adhesion molecule or CXCL12 receptor (CXCR4) expression as shown by the similar amounts of surface molecules found in transfected and wild-type U937 cells. Likewise, an equal chemotactic response to CXCL12 in vitro excluded an intrinsic defect in cell motility in clones 15S and 36.4AS. These data strongly support the notion that ANXA1 critically interferes with a leukocyte endothelial step essential for U937 cell, and possibly monocyte, transmigration both in vitro and in vivo.
14634144 Immune modulation in multiple sclerosis patients treated with the pregnancy hormone estrio 2003 Dec 1 The protective effect of pregnancy on putative Th1-mediated autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis, is associated with a Th1 to Th2 immune shift during pregnancy. The hormone estriol increases during pregnancy and has been shown to ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis. In addition, estrogens induce cytokine changes consistent with a Th1 to Th2 shift when administered in vitro to human immune cells and in vivo to mice. In a pilot trial, oral estriol treatment of relapsing remitting multiple sclerosis patients caused significant decreases in enhancing lesions on brain magnetic resonance imaging. Here, the immunomodulatory effects of oral estriol therapy were assessed. PBMCs collected longitudinally during the trial were stimulated with mitogens, recall Ags, and glatiramer acetate. Cytokine profiles of stimulated PBMCs were determined by intracellular cytokine staining (IL-5, IL-10, IL-12 p40, TNF-alpha, and IFN-gamma) and cytometric bead array (IL-2, IL-4, IL-5, IL-10, TNF-alpha, and IFN-gamma). Significantly increased levels of IL-5 and IL-10 and decreased TNF-alpha were observed in stimulated PBMC isolated during estriol treatment. These changes in cytokines correlated with reductions of enhancing lesions on magnetic resonance imaging in relapsing remitting multiple sclerosis. The increase in IL-5 was primarily due to an increase in CD4(+) and CD8(+) T cells, the increase in IL-10 was primarily due to an increase in CD64(+) monocytes/macrophages with some effect in T cells, while the decrease in TNF-alpha was primarily due to a decrease in CD8(+) T cells. Further study of oral estriol therapy is warranted in Th1-mediated autoimmune diseases with known improvement during pregnancy.
15180965 Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. 2004 Aug Interleukin-23, a recently described cytokine produced by activated antigen-presenting cells, including dendritic cells, is a p19/p40 heterodimer. The p40 subunit is shared with IL-12, the major Th1-driving cytokine, while p19 is distantly related to IL-12 p35. IL-23 has pro-inflammatory actions, inducing IL-17 secretion from activated CD4+ T cells, and stimulating the proliferation of memory CD4+ T cells. Here, we examined the effects of PGE2, a well-known immunomodulator, on the production of IL-23 by bone marrow- derived dendritic cells (BM-DCs). Our results indicate that PGE2 increases the production of functional IL-23 from immature BM-DCs in a time- and dose-dependent manner. PGE2 induces both the expression of p19 and p40, without affecting p35 expression. The effect of PGE2 is mediated through the specific receptors EP2/4 and is mimicked by cAMP-inducing agents, such as forskolin and dbcAMP. Although PGE2 also induces IL-1beta and IL-6 expression in non-stimulated DCs, the stimulatory effect of PGE2 on IL-23 production is not mediated through IL-1beta or IL-6. GM-CSF, the pro-inflammatory cytokine required for the generation of BM-DCs, amplifies the IL-23 inducing activity of PGE2 in a synergistic manner. Recent studies described both pro- and anti-inflammatory effects of PGE2, and our results suggest an additional mechanism for its pro-inflammatory role, particularly significant for autoimmune diseases, such as rheumatoid arthritis.
15301860 Identification of single nucleotide polymorphisms in the tumor necrosis factor (TNF) and T 2004 Jul The tumor necrosis factor (TNF) and TNF receptor (TNF-TNFR) superfamily plays crucial roles in immune regulation and host immune responses. The superfamily has been also associated with many immune-mediated diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease, and diabetes. In order to investigate genetic variants of the TNF-TNFR superfamily, a total of 63 known single nucleotide polymorphisms (SNPs) in the coding region (cSNPs) of the TNF-TNFR superfamily genes were selected from the public SNP database. Among 63 cSNPs tested in this study, only 24 SNPs (38%) were validated to be polymorphic in the Korean population by primer extension-based SNP genotyping. By means of the new enhanced single strand conformational polymorphism (SSCP) method, we also identified a total of 78 SNPs, including 48 known SNPs and 30 novel SNPs, in the 44 human TNF-TNFR superfamily genes. The newly discovered SNPs in the TNF-TNFR superfamily genes revealed that the Korean population had very different patterns of allele frequency compared with African or white populations, whereas Korean allele frequencies were highly similar to those of Asian (correlation coefficient r = 0.88, p < 0.046). A higher similarity of allele frequency was observed between Korean and Japanese populations (r = 0.90, p < 0.001). The validated SNPs in the TNF-TNFR superfamily would be valuable for association studies with several immune-mediated human diseases.
15289194 Bench to bedside: HMGB1-a novel proinflammatory cytokine and potential therapeutic target 2004 Aug Overwhelming gram-negative bacterial infection and life-threatening systemic inflammation are widespread problems in critically ill emergency department patients. Currently, the treatment of these patients is largely supportive, focusing on antibiotics, fluids, hemodynamic and ventilatory support, and intensive monitoring. The only Food and Drug Administration-approved pharmaceutical agent for the treatment of sepsis is activated protein C, with its use largely relegated to the intensive care unit. The subject thus remains an active area of exploration for emergency medicine research. During sepsis and inflammation, innate immune cells release excessive amounts of proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1beta. If delivered early enough, anti-TNF antibodies can be an effective therapy in experimental models of septic shock. Anti-TNF antibodies have been developed for clinical use in rheumatoid arthritis and Crohn's disease. However, anti-TNF treatment for sepsis has been difficult to achieve in the clinical setting, perhaps because TNF's early release and transient appearance in the serum create a narrow therapeutic window. An alternative strategy would be to identify "late" mediators that may be clinically more accessible. High mobility group box 1 (HMGB1), a protein previously known only as a nuclear transcription factor, is now implicated as a late mediator of sepsis. Targeting late mediators of lethal systemic inflammation represents a novel approach that may widen the therapeutic window and lead to new strategies for inhibiting the deleterious effects of the inflammatory cascade. Here the authors review the studies that led to the discovery of HMGB1 as a late mediator of systemic inflammation and discuss the possibility of HMGB1 as a therapeutic target for septic patients in the emergency department.