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Cytokines secreted by arecoline activate fibroblasts that affect the balance of TH17 and Treg
Author(s) -
Wang Liping,
Gu Liqun,
Tang Zhangui
Publication year - 2020
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12965
Subject(s) - arecoline , foxp3 , cytokine , peripheral blood mononuclear cell , flow cytometry , pathogenesis , interleukin , rar related orphan receptor gamma , il 2 receptor , immunology , immune system , chemistry , microbiology and biotechnology , biology , medicine , t cell , receptor , in vitro , biochemistry , muscarinic acetylcholine receptor
Background Oral submucous fibrosis (OSF) is a chronic progressive oral disease with cancerous tendency. Arecoline plays an important role in the pathogenesis of OSF. Fibroblasts (FBs) are the primary cells involved in the pathogenesis of OSF. There is a change in CD4 + IL‐17 + helper T cells (Th17) and CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in OSF patients, but the molecular mechanisms of are not clearly understood. In this work, we studied the molecular mechanisms. Methods Enzyme digestion was used to extract primary FBs, and immunofluorescence was used to identify FBs. Cytotoxic experiment was then performed to determine the effect of arecoline on FB activity. Enzyme‐linked immunosorbent assay (ELISA) was used to detect changes in the amount of cytokines. In addition, we treated human peripheral blood mononuclear cells (PBMC) with the above cytokines and detected their changes. Flow cytometry was used to detect the changes of Th17 and Treg, and quantitative‐polymerase chain reaction (Q‐PCR) was used to detect the changes of RORγt and Foxp3. Results We have found that the stimulation of arecoline on FBs increased interleukin‐2, interleukin‐6, and interleukin‐21 (IL‐2, IL‐6, and IL‐21) while decreased transforming growth cytokine‐β (TGF‐β). After the cytokine‐containing supernatant was co‐cultured with PBMC, the cytometry results showed that Th17 was increased, while Treg was significantly decreased and Q‐PCR results showed that RORγt expression was increased and Foxp3 expression was decreased. Conclusion The arecoline can affect inflammatory cytokines produced by FBs, which then act on immune cells Th17 and Treg, and make them change.