β2-microglobulin alters the profiles of inflammatory cytokines and of matrix metalloprotease in macrophages derived from the osteoarthritic synovium

Abstract

Several studies have implicated β 2-microglobulin (B2M) in osteoarthritis (OA) pathology. Of the main constituents of synovial tissue, synovial fibroblasts and macrophages, the latter play a pivotal role in inflammation. Although several studies have investigated the effects of B2M on synovial fibroblasts, few have examined the impact on synovial macrophages. Here, we investigated the effect of B2M on the expression profiles of inflammatory cytokines and matrix metalloproteases (MMPs) in synovial macrophages. Synovial macrophages were isolated from the osteoarthritic synovium using an anti-CD14 anti- body and magnetic isolation system. Synovial macrophages were stimulated with B2M for 6 and 24 h. Following stimulation, cell surface marker (CD80, CD163, CD206), cytokine [interleukin (IL)-6, IL-8, tumor necrosis factor α (TNF- α )] and matrix metalloprotease (MMP; MMP-9 and MMP-13) genes were evaluated by real-time PCR. Additionally, cytokine concentrations in cell culture supernatant were determined using enzyme-linked immunosorbent assay (ELISA). B2M significantly increased CD80 and decreased CD163 expression. In addition, B2M stimulation increased inflammatory cytokines at both the mRNA and protein levels. While B2M likewise elevated MMP-13 levels, there was no difference in MMP-9 expression between vehicle and B2M-treated cells. B2M increased M1 macrophage marker, inflammatory cytokine, and MMP-13 expression in synovial macrophages. B2M-related activation of synovial macrophages may thus be associated with OA pathology.

Decoding the transcriptome of muscular dystrophy due to Ptrf deficiency using single‐nucleus RNA sequencing

“…B2m and Apod genes were upregulated significantly in the Qua and Sol of Ptrf KO mice and enriched in the “Regulation of cytokine production” term. Previous studies have shown that B2m is associated with immune response and could alter the profiles of inflammatory cytokines 39–42 . Apod regulated cytokine production in the inflammatory response and influenced the cytokine/chemokine inflammatory network 43,44 .…”

“…Previous studies have shown that B2m is associated with immune response and could alter the profiles of inflammatory cytokines. [39][40][41][42] Apod regulated cytokine production in the inflammatory response and influenced the cytokine/chemokine inflammatory network. 43,44 These results suggested the involvement of the immune system and cytokines in muscular dystrophic muscle.…”

Anin vivo“turning model” reveals new RanBP9 interactions in lung macrophages

“…Its loss specifically reduces the lipopolysaccharide-induced inflammatory response of rodent alveolar macrophages [50][51][52][53][54] . Specifically in macrophages, β2-microglobulin alters inflammation osteoarthritis 55 , triggers the inflammasome activation in tumorassociated macrophages 56 , and determines the response to immunotherapy in lung adenocarcinoma 57 . Cux1 is involved in the polarization of tumor-associated macrophages by antagonizing NF-κB signaling 58 .…”