Short cytoplasmic isoform of IL1R1/CD121a mediates IL1β induced proliferation of synovium-derived mesenchymal stem/stromal cells through ERK1/2 pathway

Objectives: IL1 beta 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 IL1 beta-mediated growth promotion. Methods: 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. Results: IL1 beta 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 IL1 beta induced delayed timing of the ERK1/2 phosphorylation and I kappa B alpha degradation in synMSCs. QPCR analyses for IL1 beta-target genes indicated that cyclin D was specifically downregulated by a MAPK/ERK inhibitor, U0126, but not by a NF kappa B inhibitor, TPCA-1. In contrast, the expression of inflammatory cytokines such as IL1 alpha and IL6 are significantly decreased by TPCA-1 but less effectively decreased by U0126. Conclusion: Our data indicated that the cytoplasmic IL1R1/CD121a transduced IL1 beta signal in synMSCs. And the growth-promoting effect of IL1 beta can be separated from its inflammatory cytokine-inducing function in synMSCs.

Automated summary

IL1β enhances the proliferation of synovial mesenchymal stem/stromal cells through intracellular IL1 receptor IL1R1/CD121a, and the growth-promoting effect of IL1β can be separated from its function of inducing inflammatory cytokines in the cells.