Inflammation-dependent secretion and splicing of IL-32{gamma} in rheumatoid arthritis.

ABSTRACT: Different splice variants of the proinflammatory cytokine IL-32 are found in various tissues; their putative differences in biological function remain unknown. In the present study, we report that IL-32γ is the most active isoform of the cytokine. Splicing to one less active IL-32β appears to be a salvage mechanism to reduce inflammation. Adenoviral overexpression of IL-32γ (AdIL-32γ) resulted in exclusion of the IL-32γ-specific exon in vitro as well as in vivo, primarily leading to expression of IL-32β mRNA and protein. Splicing of the IL-32γ-specific exon was prevented by single-nucleotide mutation, which blocked recognition of the splice site by the spliceosome. Overexpression of splice-resistant IL-32γ in THP1 cells or rheumatoid arthritis (RA) synovial fibroblasts resulted in a greate

SUBMITTER: Heinhuis B 

PROVIDER: S-EPMC3064318 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature