Gene Expression Profiling of Toll-Like Receptor 4 and 5 in Peripheral Blood Mononuclear Cells of Patients with Systemic Sclerosis

Simin Almasi,Saeed Aslani,Hadi Poormoghim,Ahmadreza Jamshidi,Mahdi Mahmoudi,Shiva Poursani

doi:10.3844/ajisp.2016.10.16

Abstract

The Toll-Like Receptor (TLR) family is appeared to be expressed in many cell types in the immune system and plays a role in the pathogenesis of various autoimmune diseases. The expression profile and role of TLRs in Systemic Sclerosis (SSc) have been partly explained. It is aimed through this investigation to evaluate the expression pattern of TLR 4 and 5 in Peripheral Blood Mononuclear Cells (PBMCs) from SSc patients. PBMCs were isolated from whole blood of 20 SSc patients and 50 healthy individuals. Total RNA content of leukocytes was extracted. Then, cDNA was synthesized from the mRNA of the cells. Afterward, Quantitative analysis was carried out through Real-Time PCR using the TaqMan Gene Expression Assays. An over expression of TLR5 mRNA in PBMCs from SSc patients was seen in comparison to healthy individuals. Nevertheless, the gene expression of TLR4 in SSc patients remained almost equal to controls. Our findings suggest that over expression of TLR5 in SSc patients may be involved in the pathogenesis of SSc. Â© 2016 Simin Almasi, Saeed Aslani, Hadi Poormoghim, Ahmadreza Jamshidi, Shiva Poursani and Mahdi Mahmoudi.

Highlights

Systemic Sclerosis (SSc) is a systemic connective tissue disease, characterized by fibrosis of the skin and internal organs, injuries of the small arteries and the presence of autoantibodies (Varga and Abraham, 2007)
Toll-Like Receptor (TLR) play an essential role in the innate immune system as Pathogen-Recognition Receptors (PRRs) to recognize conserved structures within microbes known as Pathogen-Associated Molecular Patterns (PAMPs) and self-cells derived Damage-Associated Molecular Patterns (DAMPs) (Janeway Jr, 1992)
Several DAMPs in distinct pathogens are recognized by TLRs that leads to a signaling cascade and results in production of various pro-inflammatory cytokines, chemokines and type I IFNs (Akira et al, 2006)

Summary

Introduction

Systemic Sclerosis (SSc) is a systemic connective tissue disease, characterized by fibrosis of the skin and internal organs, injuries of the small arteries (microangiopathy) and the presence of autoantibodies (Varga and Abraham, 2007). A pathogenic role in the SSc has been suggested through interactions between modified endothelial cells and cells of immune system in eliciting changed fibroblast functional (Jimenez and Derk, 2004). Fibroblasts in SS are distinguished by high amount of collagen synthesis and excess fibrotic condition over degradation is thought to take place (Pattanaik et al, 2015). TLRs play an essential role in the innate immune system as Pathogen-Recognition Receptors (PRRs) to recognize conserved structures within microbes known as Pathogen-Associated Molecular Patterns (PAMPs) and self-cells derived Damage-Associated Molecular Patterns (DAMPs) (Janeway Jr, 1992). Several DAMPs in distinct pathogens are recognized by TLRs that leads to a signaling cascade and results in production of various pro-inflammatory cytokines, chemokines and type I IFNs (Akira et al, 2006)

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