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Background: Behcet's Disease (BD) is a multisystemic inflammatory disorder affecting large vessels, lungs joints, gastrointestinal and neurological systems. The pathogenesis of BD remains poorly understood. Identifying the key signaling pathway is crucial for a complete understanding of the pathogenesis of BD., Objective: The aim of this study was to determine mRNA expression level of Src family kinases (SFKs) members and their involvement in lipopolysaccharide (LPS)-induced mitogen-activated protein kinases (MAPKs) regulation in peripheral blood mononuclear cells (PBMCs) of active BD patients., Methods: Twenty- five active BD patients and twenty-five healthy controls were included in the study. PBMCs were isolated from total blood by density gradient centrifugation. The mRNA expression levels of SFKs members were measured by real-time quantitative PCR (RT-qPCR). The effect of SFKs activity on LPS-induced activation MAPKs (Erk1/2, p38 and JNK) was examined by Western blot., Results: The mRNA expression levels of Hck, Src, Lyn, Yes and Fyn were found to be slightly decreased in active BD patients compared to the control subjects, but a slight change in mRNA level of SFKs members did not impact on protein levels and protein activity. LPS-induced Erk1/2 phosphorylation was significantly increased in the absence of SFKs activity in active BD patients. However, inhibition of SFKs activity had no effect on LPS-induced phosphorylation of p38 and JNK in both controls and active BD patients., Conclusion: SFKs downregulate LPS-induced Erk1/2 phosphorylation in PBMCs of active BD patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Behçet's disease (BD) is achronic inflammatory disorder characterized by recurrent oral and genital ulcers, uveitis and skin lesions. Although,the pathogenesis of BD remains poorly understood, excessive or dysregulatedcytokine production including IL-10 is associated with BD. Revealing the key molecular mechanism by which IL-10 expression is regulated is crucial to understanding the pathogenesis of BD. The aim of this study was to investigate whether Src family kinases (SFKs) are upstream mediators of STAT3/IL-10 pathway in peripheral blood mono nuclear cells(PBMCs) of active BD patients.Twenty active BD patients and twenty healthy subjects used as control were included in the study. PBMCs were isolated from total blood by density gradient centrifugation.Western blot and ELISA methods were applied to analyzelipopolysaccharide (LPS)-induced SFKs/STAT3/IL10 signaling pathway in BD.Inhibition of SFKs activity suppressed LPS-induced IL-10 production in PBMCs fromboth controls and active BD patients. Similarly, blockage of STAT3 activation abrogated LPS-induced IL-10 production. However, LPS-induced STAT3 activation required for IL-10 production was found to be dependent on SFKs activity as LPS-induced STAT3 phosphorylation was reduced by the inhibition of SFKs activity in PBMCs of active BD patients.SFKs activity is essential for LPS-induced STAT3/IL-10 pathway in PBMCs of active BD patients. Manipulation of the SFKs activity may offer a novel therapeutic approach for BD.