Critical role of IL-1α in IL-1β-induced inflammatory responses: cooperation with NF-κBp65 in transcriptional regulation.

ABSTRACT: The IL-1 cytokines are considered among the first family of cytokines that orchestrate acute and chronic inflammatory diseases. Both IL-1β and IL-1α are members of the IL-1 family; however, their distinct roles in the inflammatory processes remain poorly understood. We explored the role of IL-1α in IL-1β-activated signaling pathways causing synovial inflammation in rheumatoid arthritis (RA). Using synovial fibroblasts isolated from RA joints, we found that IL-1β significantly stimulated IL-1α expression, which was selectively inhibited by blocking the NF-κB pathway. Knockdown of IL-1α using small interfering RNA abolished IL-1β-induced pro-IL-1α and pro-IL-1β expression and suppressed inflammation. Native and chromatin immunoprecipitation studies showed that IL-1α cooperates in NF-κBp65 bi

SUBMITTER: Singh AK 

PROVIDER: S-EPMC6338654 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature