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mRNA Expression Profile of SFKs and Involvement of SFKs in the Regulation of LPS-Induced Erk1/2 Signaling in PBMCs of Active BD Patients

[ Vol. 19 , Issue. 6 ]

Author(s):

Sevgi Irtegun-Kandemir*, Irmak Icen-Taskin, Mehtap Bozkurt and Sevgi Kalkanli-Tas   Pages 809 - 817 ( 9 )

Abstract:


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.

Method: 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.

Keywords:

Behçet’s disease, LPS, Mitogen-activated protein kinase, Src family kinases, PBMCs, TLR4.

Affiliation:

Department of Medical Biology, Faculty of Medicine, Dicle University, Diyarbakır, Department of Molecular Biology and Genetics, Faculty of Science and Art, Inönü University, Malatya, Department of Physical Therapy and Rehabilitation, Faculty of Medicine, Dicle University, Diyarbakır, Department of Immunology, Faculty of Medicine, University of Health Sciences, Istanbul



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