Joint Destructive Role of Mast Cells in Rheumatoid Arthritis [post]

Kyoung-Woon Kim, Bo-Mi Kim, Ji-Yeon Won, Hong-Ki Min, Kyung-Ann Lee, Sang-Heon Lee, HAE-RIM KIM
2020 unpublished
Background: We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods: Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with
more » ... were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results: The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FceR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase- and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions: Mast cells and their mediators such as tryptase, chymase, and histamine were increased in RA synovial tissues and fluid. Mast cells stimulated osteoclast differentiation in monocytes. The inhibition of mast cells could be a new therapeutic option for reducing joint destruction in RA.
doi:10.21203/rs.3.rs-28824/v1 fatcat:l5teo5muknfybkbm7fyxzusz3a