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ID PMID Title PublicationDate abstract
16769661 Anti-Jo-1 antibody positive polymyositis--successful therapy with leflunomide. 2006 May Idiopathic inflammatory myopathies (IM), including dermatomyositis (DM) and polymyositis (PM), are a group of systemic rheumatologic diseases of unknown etiology characterized by chronic myositis. Antisynthetase antibodies such as the anti-Jo-1 antibody are known to be highly specific for inflammatory myopathies. Patients with this antibody frequently show a combination of symptoms including interstitial lung disease, fever, polyarthritis, myositis, Raynaud's phenomenon and "mechanic's hands". In the management of PM with anti-Jo-1 antibody, immunosuppressive agents are used to control the disease. Leflunomide is a new immunosuppressive drug recently introduced in the treatment of rheumatoid and psoriatic arthritis. Here, we report two cases of female patients with PM and anti-Jo-1 antibodies, who were successfully treated with leflunomide.
19566010 The in vitro anti-denaturation effects induced by natural products and non-steroidal compo 2008 Sep There are emerging ethical issues with regards to the use of animals in the early stages of drug discovery for anti-inflammatory and degenerative diseases from natural products using the activity-directed isolation pathways when many compounds (eg > 100) are present in the crude extract or fraction and are to be tested The above-mentioned is the main reason for proposing the use of the in vitro anti-denaturation (stabilization) effects of heat treated (immunogenic) bovine serum albumin (BSA) as an assay. Current methods used for detecting and isolating a wide range of anti-inflammatory compounds in the early stages of the drug discovery process utilize a large number of animals. When BSA is heated and is undergoing denaturation, it expresses antigens associated to Type III hypersensitive reaction and which are related to diseases such as serum sickness, glomerulonephritis, rheumatoid arthritis and systemic lupus erythematosus. Thus, the assay that is being proposed should be applicable to the discovery of drugs for treating the above mentioned diseases and others, once the compounds stabilize the denaturation process.
19221962 Tobacco smoke-related diffuse lung diseases. 2008 Dec Cigarette smoking has been associated with several diffuse lung diseases in which both bronchiolar and interstitial lung inflammation appear to result from chronic tobacco smoke inhalation. These diseases occur primarily in relatively young adult smokers and include desquamative interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, and pulmonary Langerhans cell histiocytosis. Although these diseases are associated with characteristic histopathologic and radiological features, there is significant overlap among these diseases, and some smokers may exhibit features indicative of the broad spectrum of smoking-related interstitial and bronchiolar lung injury patterns. Cigarette smoking has also been associated with acute eosinophilic pneumonia, and it increases the risk of developing other fibrotic interstitial lung diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Although relatively uncommon, these smoking-related diffuse lung diseases should be recognized by clinicians as an important subset in the spectrum of interstitial lung diseases in which smoking cessation forms a central part of disease management. With the exception of acute eosinophilic pneumonia, which responds well to corticosteroid therapy, the role of corticosteroid and other immune-suppressive treatments in the management of smoking-related interstitial lung diseases is not entirely clear and is probably of limited utility, particularly in the absence of smoking cessation.
19032826 Hydroxylated estrogen metabolites influence the proliferation of cultured human monocytes: 2008 Sep INTRODUCTION: 17Beta-estradiol, estrone, and several of their hydroxylated metabolites, have been found to be significantly increased in synovial fluid of rheumatoid arthritis (RA) patients. In this study, we investigated whether the estrogen metabolites are able to exert direct effects on monocyte cell proliferation, which is important in RA synovial tissue activation and growth. METHODS: Human monocytes (THP-1) were treated with the following estrogen metabolites at different concentrations (from 10-8M, 10-9M, 10-10M to 10-11M) for 24, 48 and 72 hours: 16-hydroxyestrone (16OH-E1), 16-hydroxyestradiol (16OH-E2), 4-hydroxyestrone (4OH-E1), 4-hydroxyestradiol (4OH-E2), 2-hydroxyestrone (2OH-E1) and 2-hydroxyestradiol (2OH-E2). Monocytes were activated with interferon-gamma (INF-gamma). Cell cultures were also performed in presence of tamoxifen (10-7M) to evaluate whether the estrogen metabolites act through the estrogen receptors (ER). Cell growth was detected by MTT test and cell viability through the LDH release assay. RESULTS: 4OH-E1 and 2OH-E1 significantly increased cell growth at low concentration (10-10M), whereas they significantly reduced cell proliferation at high concentrations (10-9M). 16OH-E2 and 4OH-E2 induced opposite effects: cell proliferation at high concentration and antiproliferative action at low doses. On the contrary, 16OH-E1 and 2OH-E2 were found to be estrogen metabolites that induced cell proliferative effects for most of the tested doses. Tamoxifen caused the loss of effects on cell proliferation for almost all the metabolites. CONCLUSION: This study first demonstrates that different downstream estrogen metabolites interfere with monocyte proliferation and generally might modulate the immune response. Therefore, since estrogen metabolite/ratios are altered in the synovial fluid of RA patients, they might play important roles at least in RA synovial tissue hyperplasia.
17607976 [Asthma in elderly--diagnostic and therapeutic difficulties]. 2007 Bronchial asthma is a frequent cause of respiratory symptoms in elderly. In majority of cases asthmatic patients develop their disease before the age of 45 years, but sometimes the first episode of asthma occurs after the age of 60 years. Except for pharmacological methods, non-pharmacological therapies are recommended which include education of patients and his family and vaccination for influenza and pneumococcal infections. Two cases of bronchial asthma in patients over 60 years were analyzed. The first case illustrates coexistence of chronic heart-depending circulatory failure, complicated with episode of thromboembolic disease which occurred in the past, obesity and bronchial asthma, in 69 years old man. The second case illustrates 61 years old woman with chronic severe asthma from childhood, rheumatoid arthritis and tuberculous infection of the knee. It is known that evaluation of asthma severity in elderly is more difficult than in young people because of high frequency of comorbidities. An appropriate anti-asthmatic medication and education of patient and his family may enrich quality of live in elderly asthmatics.
17603547 Novel uses for anti-platelet agents as anti-inflammatory drugs. 2007 Dec An alteration in the character and function of platelets is manifested in patients with inflammatory diseases, and these alterations have been dissociated from the well-characterized involvement of platelets in thrombosis and haemostasis. Recent evidence reveals platelet activation is sometimes critical in the development of inflammation. The mechanisms by which platelets participate in inflammation are diverse, and offer numerous opportunities for future drug intervention. There is now acceptance that platelets act as innate inflammatory cells in immune responses, with roles as sentinel cells undergoing surveillance, responding to microbial invasion, orchestrating leukocyte recruitment, and migrating through tissue, causing damage and influencing repair processes in chronic disease. Some of these processes are targeted by drugs that are being developed to target platelet participation in atherosclerosis. The actions of platelets therefore influence the pathogenesis of diverse inflammatory diseases in various body compartments, encompassing parasitic and bacterial infection, allergic inflammation (especially asthma and rhinitis), and non-atopic inflammatory conditions, for example, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and atherosclerosis. This review will first discuss the evidence for platelet activation in these various inflammatory diseases, and secondly discuss the mechanisms by which this pathogenesis occurs and the various anti-platelet agents which have been developed to combat platelet activation in atherosclerosis and their potential future use for the treatment of other inflammatory diseases.
17502864 Reactivation of latent tuberculosis by TNF blockade: the role of interferon gamma. 2007 May Tumor necrosis factor (TNF) plays a pathogenic role in psoriasis and rheumatoid arthritis but is essential for host defenses against mycobacteria and other granulomatous pathogens. The risk of reactivation of latent Mycobacterium tuberculosis infection is significantly greater with the TNF monoclonal antibody infliximab than with the soluble TNF-receptor etanercept. We have examined the biologic basis of this difference using whole blood culture. Infliximab and adalimumab reduced the proportion of T buciclate-responsive cells by 70 and 50%, respectively, and suppressed antigen-induced IFN-gamma production by 70 and 64%. In contrast, etanercept produced no significant effect. The difference between infliximab and etanercept remained whether one compared equal or peak therapeutic drug concentrations, suggesting a relationship to mechanism of action rather than pharmacokinetics. Adalimumab and etanercept caused divergent, concentration dependent effects on control of intracellular growth of M. tuberculosis. None of the drugs induced significant levels of apoptosis or necrosis in monocytes or T cells, excluding T-cell death as a mechanism for suppression of antigen-induced responses. IL-10 production was equally suppressed by all three drugs, excluding excess IL-10 as a regulatory mechanism. The tuberculosis risk posed by infliximab may reflect its combined effects on TNF and IFNgamma.
17447122 Decreased proliferation and erythroid differentiation of K562 cells by siRNA-induced depre 2007 Sep PURPOSE: Recently, it was reported that OCTN1 transporter (SLC22A4) is associated with rheumatoid arthritis (RA) and Crohn's disease. Additionally, we reported that OCTN1 is expressed in hematopoietic cells, preferentially in erythroid cells. Accordingly, we assessed the physiological role of OCTN1 by examining the effect of knockdown of OCTN1 in blood cells using siRNA method. MATERIALS AND METHODS: Vector-based short hairpin RNA (shRNA) was used to establish K562 cell line which shows stably decreased expression of OCTN1. The characteristic of knockdown of OCTN1 in K562 cells was investigated by cell proliferation, cell differentiation, and uptake of ergothioneine that is a good substrate of OCTN1. RESULTS: Several clones of K562 cells exhibited significantly reduced expression of OCTN1 mRNA and protein. They also showed a decreased growth rate and butyrate-dependent differentiation to erythrocytes compared with control-vector transfected cells. In addition, uptake of [(3)H]ergothioneine by K562 cells suggested that Na(+)-dependent and high-affinity transporter which is similar to the characteristics of OCTN1 is functional. Moreover, uptake of ergothioneine by K562 cells which exhibit decreased-expression of OCTN1 was decreased in comparison with wild type K562 cells. CONCLUSIONS: It was suggested that OCTN1 is involved in the transport of physiological compounds that are important for cell proliferation and erythroid differentiation.
19454084 NSAIDs. 2007 Jun 1 INTRODUCTION: NSAIDs are widely used. Almost 10% of people in The Netherlands used a non-aspirin NSAID in 1987, and the overall use was 11 defined daily doses per 1000 population per day. In Australia in 1994, overall use was 35 defined daily doses per 1000 population a day, with 36% of the people receiving NSAIDs for osteoarthritis, 42% for sprain and strain or low back pain, and 4% for rheumatoid arthritis; 35% of the people receiving NSAIDs were aged over 60 years. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: Are there any important differences between NSAIDs? What are the effects of topical NSAIDs; and of co-treatments to reduce the risk of gastrointestinal adverse effects of NSAIDs? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the benefits and harms of the following interventions: alternative analgesics, H(2) blockers, misoprostol, NSAIDs (systemic, topical, differences in efficacy between, dose-response relationship of), proton pump inhibitors.
16987757 Transient exposure of fibroblast growth factor-2 induced proliferative but not destructive 2006 Fibroblast growth factor-2 (FGF-2) has the potential to regenerate damaged articular cartilage tissue due to its exerting anabolic effects on chondrocytes. However, FGF-2 is involved in pathogenesis of rheumatoid arthritis, where the joint is destructed. The study aims at clarifying the effects of FGF-2 on joints. When radiolabeled FGF-2 was injected into knee joints of C57Bl/10 mice, a transient binding was observed in the superficial and intermediate zones of the articular cartilage as well as in the synovium and perichondrium. An FGF-2 injection (5 microg) caused synovial hyperplasia adjacent to the articular cartilage on day 7, cartilage formation adjacent to the articular cartilage on day 14, and osteophyte on day 21. The intensity of safranin-O staining of the articular cartilage increased on day 14. These changes were dose-dependent. No destructive changes in the joints were observed. In a joint, transient exposure of FGF-2 caused proliferative changes, but not destructive changes.
20641599 Cyclo(-Arg-Gly-Asp-d-Phe-Lys(([(18)F]Fluoropropionyl)galacto-amino acid)-). 2004 Integrins are a family of heterodimeric cell surface glycoproteins consisting of an α and a β subunit. Integrins mediate diverse biological events involving cell-cell and cell-matrix interactions (1) and are important for cell adhesion and signal transduction. Integrin α(v)β(3) is the most prominent receptor class, affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). It is strongly expressed on tumor cells and activated endothelial cells, whereas it is weakly expressed on resting endothelial cells and most normal tissues. Antagonists to integrin α(v)β(3) are being studied as antitumor and antiangiogenic agents (4, 8, 9), and agonists are being studied as angiogenic agents for coronary angiogenesis (10, 11). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (12); however, these RGD analogs are lipophilic and concentrate in the liver. To reduce the lipophilicity of the peptide, Haubner et al. (13, 14) conjugated a sugar molecule to a cyclic RGD peptide to produce cyclo(-Arg-Gly-Asp-d-Phe-Lys(([(18)F]fluoropropionyl)galacto-amino acid)-) ([(18)F]Galacto-RGD) for use in positron emission tomography (PET) imaging studies.
18626814 Th17 cells: a new therapeutic target in inflammatory dermatoses. 2008 Th17 cells, named for their secretion of interleukin-17 (IL-17), are a new class of T-cells involved in a wide range of cutaneous autoimmune and inflammatory conditions. An overactive Th17 cell response in the skin can produce damaging results. There appears to be a partial role for the Th17 axis in the pathogenesis of a range of dermatological diseases including allergic contact dermatitis, atopic dermatitis, psoriasis, and scleroderma. Immunologists have also discovered a unique association between Th17 cells and cutaneous T-cell lymphoma. The Th17 branch has been linked to a number of additional systemic inflammatory diseases with significant cutaneous pathology such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and Behcet's disease. Newly developed treatment modalities for neutralizing the Th17 branch of the immune system are proving to be valuable additions to the current therapeutic armamentarium.
18581240 Assessment of the impact of dosing time on the pharmacokinetics/pharmacodynamics of predni 2008 Jun Prednisolone is widely used for the treatment of inflammation and auto-immune diseases. It exhibits nonlinear pharmacokinetics (PK); and its induced systemic effects (pharmacodynamics (PD)) are commonly evaluated with two biomarkers, cortisol and blood lymphocytes in plasma. Circadian patterns are observed in both biomarkers. Furthermore, the disease itself may show a circadian pattern. For example, in rheumatoid arthritis patients, better therapeutic outcomes have been reported when prednisolone was administered in the very early morning. The aim of this study is to evaluate the impact of dosing time on the PK/PD of prednisolone with a simulation approach using an interactive algorithm. A series of simulations were performed with either intravenous or oral administration of prednisolone or prednisone. The results showed that the initial or maximum concentration and trough concentration of total prednisolone were lower when the drug was administered in the early morning around 6 AM: . Oscillation patterns were observed in cumulative cortisol suppression (CCS) and alteration of total lymphocyte trafficking in blood. When the drug was given in the morning within the therapeutic dose range, or around 6 PM: for a small dose amount (<1 mg), the minimum CCS and maximum effect on lymphocytes were observed. These results indicated that the PK/PD of prednisolone are time- and dose-dependent, and suggested that it is necessary to consider the application of chronotherapy to achieve better clinical outcomes with fewer side effects of prednisolone, and a PK/PD simulation approach could provide a valuable tool to evaluate and predict time-dependency in the system.
18560920 Priority-setting tools for rheumatology disease referrals: a review of the literature. 2008 Nov As part of a larger body of work to develop a rheumatology priority referral score, a literature review was conducted. The objective of the literature review was to identify preexisting priority-setting, triage, and referral tools/scales developed to guide referrals from primary care to specialist care/consultation usually provided by a rheumatologist. Using a combination of database, citation, Internet, and hand-searching, 20 papers were identified that related to referral prioritization in three areas: rheumatoid arthritis (RA; 5), musculoskeletal (MSK) diseases other than RA (3), and MSK diseases in general (12). No single set of priority-setting criteria was identified for rheumatologic disorders across the spectrum of patients who may be referred from primary care providers (PCPs) to rheumatologists. There appears to be more congruence on conditions at either end of the urgency spectrum with conditions such as suspected cranial arteritis or systemic vasculitis deemed to be emergency referrals and fibromyalgia and other soft-tissue syndromes deemed to be more routine referrals. Between these two extremes, there is a divergence of opinion about urgency and few papers on the issue. The exception to this is referral for early RA for which several criteria have been established. Despite the inherent complexities in developing a tool to prioritize patients referred by PCPs to rheumatologists, there are compelling reasons to proceed. With the aging of the population, the number of patients being referred to rheumatologists is expected to increase. With pharmaceutical advances, there are demonstrable benefits in early referral for some conditions. These trends have led to increased pressure on scarce rheumatological human resources. A tool to prioritize referrals is a critical component of improving access and the referral process.
18549931 Parvovirus B19 infection and systemic lupus erythematosus: Activation of an aberrant pathw 2008 Jul Parvovirus B19 infection has been associated with a variety of rheumatic manifestations/diseases, mainly rheumatoid arthritis, vasculitis and systemic lupus erythematosus (SLE). B19 infection may simulate both clinical and laboratory features of SLE, presenting either as a potential first time diagnosis of SLE or as an exacerbation of previously established disease. The similarities in both clinical and serological features of parvovirus infection and SLE at presentation may hinder the differential diagnosis between these two conditions. Hence, parvovirus B19 infection mimicking SLE usually fulfils <4 ACR criteria for SLE, rarely includes cardiac or renal involvement or presents with haemolytic anaemia, and is usually associated with short-lived, low titers of autoantibodies. Rarely, cases of multisystemic involvement solely attributed to a recent parvovirus B19 infection have been reported, rendering early accurate diagnosis of particular importance and justifying the screening for evidence of parvovirus B19 involvement in newly diagnosed cases of SLE, especially the ones with abrupt onset of symptoms along with cases of SLE flares. This review describes basic features of parvovirus B19 structure and pathogenicity and expands on the parvo-associated auto-immune manifestations particularly in relation to SLE-mimicking or SLE-triggering reported cases. The proposed mechanisms for viral-induced pathologic autoimmunity are discussed with emphasis on emerging data regarding the aberrant expression and localization of autoantigens and their potential implication in alternatively activated immunological cascades.
18466536 Joint modeling of linkage and association using affected sib-pair data. 2007 There has been a growing interest in developing strategies for identifying single-nucleotide polymorphisms (SNPs) that explain a linkage signal by joint modeling of linkage and association. We compare several existing methods and propose a new method called the homozygote sharing transmission-disequilibrium test (HSTDT) to detect linkage and association or to identify SNPs explaining the linkage signal on chromosome 6 for rheumatoid arthritis using 100 replicates of the Genetic Analysis Workshop (GAW) 15 simulated affected sib-pair data. Existing methods considered included the family-based tests of association implemented in FBAT, a transmission-disequilibrium test, a conditional logistic regression approach, a likelihood-based approach implemented in LAMP, and the homozygote sharing test (HST). We compared the type I error rates and power for tests classified into three categories according to their null hypotheses: 1) no association in the presence of linkage (i.e., a SNP explains none of the linkage evidence), 2) no linkage adjusting for the association (i.e., a SNP explains all linkage evidence), and 3) no linkage and no association. For testing association in the presence of linkage, we found similar power among all tests except for the homozygote sharing test that had lower power. When testing linkage adjusting for association, similar power was observed between LAMP and HST, but lower power for the conditional logistic regression method. When testing linkage or association, the conditional logistic regression method was more powerful than FBAT.
18413445 Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increa 2008 Oct OBJECTIVES: A gene-environment interaction between HLA-DR shared epitope genes and smoking in anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis (RA) has been reported. Identification of citrullinated proteins in bronchoalveolar lavage (BAL) cells from smokers has led to the suggestion that citrullination induced by smoking might be the first step in the pathogenic chain of RA. OBJECTIVE: To confirm and extend these findings. METHODS: Immunohistochemistry was performed on BAL cells and bronchial mucosal biopsy sections obtained through bronchoscopy from 14 healthy smokers and 16 healthy non-smokers. Two antibodies recognising citrullinated proteins, two antibodies recognising peptidylarginine deiminase (PAD)2 enzyme and one recognising PAD4 enzyme were used. RESULTS: Citrullinated proteins are upregulated in BAL cells of healthy smokers compared with healthy non-smokers. This was associated with higher expression of the PAD2 enzyme. The same level of citrullinated proteins was present in bronchial mucosal biopsy specimens of healthy smokers and non-smokers, despite higher expression of PAD2 in smokers. CONCLUSION: This study provides evidence that smoking enhances PAD2 expression in the bronchial mucosal and alveolar compartment, with consequent generation of citrullinated proteins in the latter. Smoking is an environmental factor that may lead to citrulline autoimmunity in genetically susceptible subjects.
18407359 Novel pharmacological strategies for driving inflammatory cell apoptosis and enhancing the 2008 May Resolution of inflammation requires the effective downregulation of key inflammatory cells such as neutrophils and eosinophils, which normally undergo programmed cell death (apoptosis) to enable their detection and removal by phagocytes such as macrophages. Dysregulation of this process is thought to contribute to the pathogenesis and progression of chronic inflammatory disorders such as chronic obstructive pulmonary disease, asthma, rheumatoid arthritis, allergic rhinitis and inflammatory bowel disease. Importantly, knowledge of the signalling pathways responsible for the induction and execution of granulocyte apoptosis and the phagocytic removal of apoptotic cells continues to increase and, with it, the potential for incisive pharmacological intervention. In this article, we highlight pharmacological strategies that could be used to drive the resolution of inflammation by augmenting apoptosis of inflammatory cells.
18402977 Quantitative determination of humanized monoclonal antibody rhuMAb2H7 in cynomolgus monkey 2008 Jun 1 Preclinical pharmacokinetic (PK) assays are important to help evaluate the safety and efficacy of a potential biotherapeutic before clinical studies. The assay typically requires a biotherapeutic-specific reagent to minimize matrix effects especially when the host species are non-human primates such as cynomolgus monkeys and the biotherapeutic is a humanized monoclonal antibody (MAb). Recombinant humanized mAb 2H7 (rhuMAb2H7) binds to the extracellular domain of CD20 that is expressed on B cells and results in B cell depletion. It is currently being evaluated for its therapeutic potential in rheumatoid arthritis (RA) in clinical studies. During the early development of rhuMAb2H7, a cynomolgus monkey PK assay was needed to help assess the pharmacokinetic parameters of rhuMAb2H7 in a pilot cynomolgus monkey study. However, development of a cynomolgus monkey PK assay was challenging due to lack of rhuMAb2H7-specific reagents. Here we describe an alternative method for detection of rhuMAb2H7 in cynomolgus monkey serum using polyclonal antibodies against human IgGs. This assay quantifies rhuMAb2H7 in 10% cynomolgus monkey serum with high sensitivity, accuracy, and precision. This assay successfully supported the rhuMAb2H7 development, and has the potential to be used to quantify other humanized MAb biotherapeutics in serum from a variety of non-human species.
18266978 Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health 2008 Jun Angiopoietin-1 (Ang-1) is the primary agonist for Tie2 tyrosine kinase receptor (Tie2), and the effect of Ang-1-Tie2 signalling is context-dependent. Deficiency in either Ang-1 or Tie2 protein leads to severe microvascular defects and subsequent embryonic lethality in murine model. Tie2 receptors are expressed in several cell types, including endothelial cells, smooth muscle cells, fibroblasts, epithelial cells, monocytes, neutrophils, eosinophils and glial cells. Ang-1-Tie2 signalling induces a chemotactic effect in smooth muscle cells, neutrophils and eosinophils, and induces differentiation of mesenchymal cells to smooth muscle cells. Additionally, this signalling pathway induces the secretion of serotonin, matrix metalloproteinases (MMPs) and plasmin. Ang-1 inhibits the secretion of tissue inhibitor of matrix metalloproteinase (TIMPs). Aberrant expression and activity of Tie2 in vascular and non-vascular cells may result in the development of rheumatoid arthritis, cancer, hypertension and psoriasis. Ang-1 has an anti-inflammatory effect, when co-localized with vascular endothelial growth factor (VEGF) in the vasculature. Thus, Ang-1 could be potentially important in the therapy of various pathological conditions such as pulmonary hypertension, arteriosclerosis and diabetic retinopathy. In this article, we have summarized and critically reviewed the pathophysiological role of Ang-1-Tie2 signalling pathway.