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IL1β enhances proliferation of synovial mesenchymal stem/stromal cells (synMSCs) although they don't express its receptor, IL1R1/CD121a, on the cell surface. This study was aimed to elucidate the underlying mechanisms of IL1β-mediated growth promotion. Human synMSCs were isolated from the suprapatellar synovial membrane. Cell proliferation was measured by MTT. Flowcytometric analyses were performed for surface antigen expression. Intracellular signaling pathway was analyzed by western blotting, immunocytochemistry and Q-PCR. IL1β enhanced proliferation through IL1R1/CD121a because IL1 receptor antagonist (IL1Ra) completely inhibited it. Expression analyses indicated that a short isoform of IL1R1/CD121a is expressed in synMSCs. Immunocytochemistry indicated that IL1R1/CD121a was majorly localized to the cytoplasm. Western blotting indicated that IL1β induced delayed timing of the ERK1/2 phosphorylation and IκBα degradation in synMSCs. Q-PCR analyses for IL1β-target genes indicated that cyclin D was specifically downregulated by a MAPK/ERK inhibitor, U0126, but not by a NFκB inhibitor, TPCA-1. In contrast, the expression of inflammatory cytokines such as IL1α and IL6 are significantly decreased by TPCA-1 but less effectively decreased by U0126. Our data indicated that the cytoplasmic IL1R1/CD121a transduced IL1β signal in synMSCs. And the growth-promoting effect of IL1β can be separated from its inflammatory cytokine-inducing function in synMSCs. © 2022 The Authors.


Guo Tang, Yoshinori Asou, Etsuko Matsumura, Yusuke Nakagawa, Kazumasa Miyatake, Hiroki Katagiri, Tomomasa Nakamura, Hideyuki Koga, Keiichiro Komori, Ichiro Sekiya, Yoich Ezura, Kunikazu Tsuji. Short cytoplasmic isoform of IL1R1/CD121a mediates IL1β induced proliferation of synovium-derived mesenchymal stem/stromal cells through ERK1/2 pathway. Heliyon. 2022 May;8(5):e09476

PMID: 35647352

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