Cholinergic agonists inhibit proliferation of human fibroblast-like synoviocytes and monocytic cell lines and reduce VEGF and MMPs expression by these cells.

Cholinergic agonists inhibit proliferation of human fibroblast-like synoviocytes and monocytic cell lines and reduce VEGF and MMPs expression by these cells.:

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Cholinergic agonists inhibit proliferation of human fibroblast-like synoviocytes and monocytic cell lines and reduce VEGF and MMPs expression by these cells.

Immunopharmacol Immunotoxicol. 2020 Apr 05;:1-9

Authors: Arshadi D, Shakiba Y, Rajabian A, Nikbin B, Mousavi SH, Boroushaki MT

Abstract

Background and purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Excessive proliferation of fibroblast-like synoviocytes (FLS) and over-expression of angiogenic factors play a crucial role in pannus formation and joint destruction in RA. Clarification of the role of cholinergic agonists in modulation of inflammation and immune system reactions is progressively ongoing. In this study, the anti-angiogenic effect of two cholinergic agonists, nicotine and ARR17779, on human FLS, and monocytic cell lines (U937) was evaluated.Experimental approach: The cells were cultured in DMEM supplemented with 10% FBS and treated with different doses of nicotine and ARR17779 in the presence of TNF-α, LPS, and IFN-γ. After 48 h, cell number was counted in different groups. After RNA extraction, cDNA was synthesized and the expression of VEGF and MMPs has been evaluated by real-time PCR using specific primers and probes. VEGF was assayed in U937 cell line supernatant using ELISA method.Key results: Both nicotine and ARR17779 inhibited FLS and U937 cell proliferation. Cholinergic agonists reduced the expression of MMPs and VEGF. VEGF level in supernatant of U937 cells treated with cholinergic agonists was also reduced.Conclusion and implications: Our results suggest that cholinergic agonists can modulate pathological conditions related to pannus formation in in-vitro conditions. Based on these results, cholinergic agonists can be considered as novel therapeutic options in RA. Further animal studies are needed before introducing these agents into clinical uses.

PMID: 32248717 [PubMed - as supplied by publisher]