Most cited article - PubMed ID 28446208
Calgizzarin (S100A11): a novel inflammatory mediator associated with disease activity of rheumatoid arthritis
S100A11 (calgizzarin), a member of S100 family, is associated with several autoimmune diseases, including rheumatoid arthritis (RA). Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of RA and in the externalization of some S100 family members. Therefore, we aimed to determine the association between S100A11 and NETs in RA. For this purpose, the levels of S100A11 and NETosis markers were detected in the RA synovial fluid by immunoassays. The expression of S100A11 by neutrophils in the RA synovial tissue was assessed. Neutrophils isolated from peripheral blood were exposed to S100A11 or stimulated to release NETs. The levels of NETosis- and inflammation-associated proteins were analysed by immunoassays. NETs were visualized by immunofluorescence. We showed that S100A11 was expressed by the neutrophils in the RA synovial tissue. Moreover, S100A11 in the RA synovial fluid correlated with several NETosis markers. In vitro, S100A11 was abundantly released by neutrophils undergoing NETosis compared to untreated cells (p < 0.001). Extracellular S100A11 increased the secretion of IL-6 (p < 0.05) and TNF (p < 0.05) by neutrophils but did not induce NETosis. This study demonstrates, for the first time, that the release of S100A11 is dependent on NETosis and that extracellular S100A11 augments the inflammatory response by inducing pro-inflammatory cytokines in neutrophils.
- MeSH
- Adult MeSH
- Extracellular Traps metabolism MeSH
- Interleukin-6 metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Neutrophils metabolism pathology MeSH
- S100 Proteins metabolism MeSH
- Arthritis, Rheumatoid metabolism pathology MeSH
- Aged MeSH
- Synovial Fluid metabolism MeSH
- Tumor Necrosis Factor-alpha metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- IL6 protein, human MeSH Browser
- Interleukin-6 MeSH
- S100 Proteins MeSH
- S100A11 protein, human MeSH Browser
- Tumor Necrosis Factor-alpha MeSH
S100 proteins are involved in the pathogenesis of sporadic colorectal carcinoma through different mechanisms. The aim of our study was to assess tissue mRNA encoding S100 proteins in patients with non-advanced and advanced colorectal adenoma. Mucosal biopsies were taken from the caecum, transverse colon and rectum during diagnostic and/or therapeutic colonoscopy. Another biopsy was obtained from adenomatous tissue in the advanced adenoma group. The tissue mRNA for each S100 protein (S100A4, S100A6, S100A8, S100A9, S100A11 and S100P) was investigated. Eighteen biopsies were obtained from the healthy mucosa in controls and the non-advanced adenoma group (six individuals in each group) and thirty biopsies in the advanced adenoma group (ten patients). Nine biopsies were obtained from advanced adenoma tissue (9/10 patients). Significant differences in mRNA investigated in the healthy mucosa were identified between (1) controls and the advanced adenoma group for S100A6 (p = 0.012), (2) controls and the non-advanced adenoma group for S100A8 (p = 0.033) and (3) controls and the advanced adenoma group for S100A11 (p = 0.005). In the advanced adenoma group, differences between the healthy mucosa and adenomatous tissue were found in S100A6 (p = 0.002), S100A8 (p = 0.002), S100A9 (p = 0.021) and S100A11 (p = 0.029). Abnormal mRNA expression for different S100 proteins was identified in the pathological adenomatous tissue as well as in the morphologically normal large intestinal mucosa.
- Keywords
- S100 proteins, colorectal neoplasia, large intestine, mRNA,
- MeSH
- Adenoma genetics metabolism pathology MeSH
- Calgranulin A genetics metabolism MeSH
- Calgranulin B genetics metabolism MeSH
- Colorectal Neoplasms genetics metabolism pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger genetics metabolism MeSH
- Biomarkers, Tumor genetics metabolism MeSH
- Neoplasm Proteins genetics metabolism MeSH
- Follow-Up Studies MeSH
- Pilot Projects MeSH
- Prognosis MeSH
- S100 Calcium Binding Protein A6 genetics metabolism MeSH
- Cell Cycle Proteins genetics metabolism MeSH
- S100 Proteins genetics metabolism MeSH
- Calcium-Binding Proteins genetics metabolism MeSH
- S100 Calcium-Binding Protein A4 genetics metabolism MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Calgranulin A MeSH
- Calgranulin B MeSH
- RNA, Messenger MeSH
- Biomarkers, Tumor MeSH
- Neoplasm Proteins MeSH
- S100 Calcium Binding Protein A6 MeSH
- Cell Cycle Proteins MeSH
- S100 Proteins MeSH
- Calcium-Binding Proteins MeSH
- S100 Calcium-Binding Protein A4 MeSH
- S100A11 protein, human MeSH Browser
- S100A4 protein, human MeSH Browser
- S100A6 protein, human MeSH Browser
- S100A8 protein, human MeSH Browser
- S100A9 protein, human MeSH Browser
- S100P protein, human MeSH Browser