LAIR ‐1 shedding from human fibroblast‐like synoviocytes in rheumatoid arthritis following TNF‐α stimulation

This study examined the expression of the inhibitory receptor, leukocyte‐associated immunoglobulin (Ig)‐like receptor‐1 (LAIR‐1) in fibroblast‐like synoviocytes (FLS) in rheumatoid arthritis (RA) patients to investigate its potential role in the modulation of inflammatory cytokines, metalloproteinases (MMPs), and invasiveness of synoviocytes. LAIR‐1 expression in synovial tissues from RA patients, osteoarthritis patients, and healthy donors was analyzed by immunohistochemistry. The membrane‐bound form (mLAIR‐1) was detected by flow cytometry. Factors involved in inflammation and MMP activity in FLS were analyzed by qPCR. LAIR‐1 expression was higher in the synovia of the RA patients than those of the osteoarthritis patients. Co‐immunostaining of vimentin/LAIR‐1 demonstrated that LAIR‐1 was mainly localized in FLS in the RA patients. Surprisingly, primary FLS isolated from the RA patients had low levels of mLAIR‐1 expression, with cytoplasmic distribution. The extracellular domain of LAIR‐1 was shed from the cell surface in response to TNF‐α, and this process could be blocked by serine protease inhibitors. Additional experiments indicated that LAIR‐1 overexpression considerably reduced FLS invasion, which simultaneously reduced the mRNA levels of IL‐6, IL‐8, and MMP‐13 in the presence of TNF‐α. Our study demonstrated that LAIR‐1 is an anti‐inflammatory molecule, and it was upregulated in FLS in the RA patients; however, cell‐surf...
Source: Clinical and Experimental Immunology - Category: Allergy & Immunology Authors: Tags: Original Article Source Type: research