Differences of IL-1β Receptors Expression by Immunocompetent Cells Subsets in Rheumatoid Arthritis.

Alina A Alshevskaya,Nadezhda S Shkaruba,Vladimir A Kozlov,Oksana A Chumasova,Sergey V Sennikov,Aleksey E Sizikov,Julia A Lopatnikova,Aleksander V Karaulov

doi:10.1155/2015/948393

Alina A Alshevskaya, Nadezhda S Shkaruba + Show 6 more

Open Access

https://doi.org/10.1155/2015/948393

Copy DOI

Abstract

IL-1β is involved in the induction and maintenance of chronic inflammation in rheumatoid arthritis (RA). Its activity is regulated and induced by soluble and membrane-bound receptors, respectively. The effectiveness of the cytokine depends not only on the percentage of receptor-positive cells in an immunocompetent subset but also on the density of receptor expression. The objective of this study was to investigate the expression of IL-1β membrane-bound receptors (IL-1R1 and IL-1R2) in terms of the percentage of receptor-positive cells and the number of receptors per cell in different subsets of immune cells in RA patients before and after a course of basic (excluding anticytokine) therapy and in healthy individuals. The resulting data indicate differences in the expression of IL-1β receptors among T cells, B cells, and monocytes in healthy volunteers and in rheumatoid arthritis patients. The importance of determining both the relative percentage of cells expressing receptors to immunomodulatory cytokines and the number of membrane-bound receptors per cell is highlighted by evidence of unidirectional or multidirectional changing of these parameters according to cell subset and health status.

Highlights

Rheumatoid arthritis (RA) is characterized by chronic systemic autoimmune inflammation of the connective tissue and is mostly accompanied by lesions in peripheral joints, erosion and degenerative changes in joints, and joint ankylosis [1]
IL-1β, which plays a key role in both the development and severity of the pathological process in RA, one needs to assess expression of types 1 and 2 receptors on cells involved in the pathology
We demonstrated that the percentage of cells expressing IL-1R1 is higher than the percentage of IL-1R2+ cells among T and B cells and monocytes only in healthy donors; after the cells are cultured, this percentage is higher among monocytes in all the groups under study

Summary

Introduction

Rheumatoid arthritis (RA) is characterized by chronic systemic autoimmune inflammation of the connective tissue and is mostly accompanied by lesions in peripheral joints, erosion and degenerative changes in joints, and joint ankylosis [1]. As a broad-spectrum proinflammatory cytokine, interleukin-1β (IL-1β) is involved in the development of both local and systemic inflammation in rheumatoid arthritis [7, 8]. IL-1β implements its biological effects after binding specific membrane-bound receptors. There are two types of membrane-bound IL-1β receptors (IL-1R1 and IL-1R2); IL-1R2 does not contain a full-fledged cytoplasmic domain. IL-1β produces its biological activity against cells only through type 1 receptor [11, 12]; the signaling pathways can be initiated only if the interleukin-1 receptor accessory protein (IL1RAcP) is present in the receptor-cytokine complex. Cytokine activity is regulated by the circulating interleukin-1 receptor antagonist (raIL-1) that competes for binding to receptors, acting as a specific IL1 inhibitor [13, 14]. Soluble IL-1 receptors are the extracellular domains of membrane-bound IL-1 receptors [15, 16], which are formed either via proteolytic cleavage catalyzed by specific

Objectives

Methods

Results

Discussion

Conclusion