Calgizzarin (S100A11): a novel inflammatory mediator associated with disease activity of rheumatoid arthritis

Abstract

BackgroundCalgizzarin (S100A11) is a member of the S100 protein family that acts in different tumors by regulating a number of biologic functions. Recent data suggest its association with low-grade inflammation in osteoarthritis (OA). The aim of our study is to compare S100A11 expression in the synovial tissues, synovial fluid and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to characterize the potential association between S100A11 and disease activity.MethodsS100A11 protein expression was detected in synovial tissue from patients with RA (n = 6) and patients with OA (n = 6) by immunohistochemistry and immunofluorescence. Serum and synovial fluid S100A11 levels were measured by ELISA in patients with RA (n = 40) and patients with OA (n = 34). Disease activity scores in 28 joints based on C-reactive protein (DAS28-CRP) were used to assess disease activity. Cytokine content in peripheral blood mononuclear cells (PBMCs), synovial fibroblasts (SFs) and synovial fluid was analysed by ELISA, western blotting or cytometric bead array.ResultsS100A11 expression was significantly up-regulated in the synovial lining and sublining layers (p < 0.01) and vessels (p < 0.05) of patients with RA compared to patients with OA, and was associated with fibroblasts and T cells. S100A11 was significantly increased in synovial fluid (p < 0.0001) but not in serum (p = 0.158) from patients with RA compared to patients with OA when adjusted for age and sex. Synovial fluid S100A11 correlated with DAS28 (r = 0.350, p = 0.027), serum CRP (r = 0.463, p = 0.003), synovial fluid leukocyte count (r = 0.677, p < 0.001), anti-cyclic citrullinated peptide antibodies (anti-CCP) (r = 0.424, p = 0.006) and IL-6 (r = 0.578, p = 0.002) and IL-8 (r = 0.740, p < 0.001) in synovial fluid from patients with RA. PBMCs and SFs isolated from patients with RA synthesized and spontaneously secreted higher levels of S100A11 in comparison with PBMCs and SFs from patients with OA (p = 0.011 and 0.03, respectively). S100A11 stimulated the production of the pro-inflammatory cytokine IL-6 by PBMCs (p < 0.05) and SFs (p < 0.01).ConclusionsOur data provide the first evidence of S100A11 up-regulation and its association with inflammation and disease activity in patients with RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1288-y) contains supplementary material, which is available to authorized users.

Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes

“…The three top markers common to old cells were the genes Aw112010 , S100a11 , and Izumo1r (AUC > 0.66 and power > 0.33; Fig. 1G), which were recently reported to be up-regulated under chronic inflammatory conditions ( 23 – 25 ). These genes imply a strong relationship between the inflammatory state and the identity of CD4 T cells in aging and can be used as general markers for aged CD4 T cells.…”

Genome-wide pQTL analysis of protein expression regulatory networks in the human liver

“…ADH1C protein is involved in alcohol metabolism and associated with alcohol dependence [ 22 , 32 ]. S100A11 belongs to the S100 protein family and is a known inflammatory factor [ 33 ]. SERPINC1 is a member of the serpin superfamily and a plasma protease inhibitor; it inhibits thrombin and acts as an anti-inflammatory factor [ 34 ].…”

Tissue mRNA for S100A4, S100A6, S100A8, S100A9, S100A11 and S100P Proteins in Colorectal Neoplasia: A Pilot Study

“…S100A11, also known as S100C or calgizzarin, has been reported to contribute to inflammatory processes [ 42 ] and multiple neoplastic events in different types of cancers, including papillary thyroid cancer [ 43 ], ovarian cancer [ 44 ], cholangiocarcinoma [ 45 ], pancreatic carcinoma [ 46 , 47 ] and gastric cancer [ 48 ]. Takamatsu et al concluded that extracellular S100A11 contributes significantly to the spread of the fibroblast population in pancreatic cancer, thus becoming a potential therapeutic target [ 49 ].…”