Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production - PubMed (original) (raw)

. 1997 Apr 10;386(6625):619-23.

doi: 10.1038/386619a0.

S Banerjee, M Hugunin, D Butler, L Herzog, A Carter, L Quintal, L Sekut, R Talanian, M Paskind, W Wong, R Kamen, D Tracey, H Allen

Affiliations

Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production

T Ghayur et al. Nature. 1997.

Abstract

Interferon-gamma-inducing factor (IGIF, interleukin-18) is a recently described cytokine that shares structural features with the interleukin-1 (IL-1) family of proteins and functional properties with IL-12. Like IL-12, IGIF is a potent inducer of interferon (IFN)-gamma from T cells and natural killer cells. IGIF is synthesized as a biologically inactive precursor molecule (proIGIF). The cellular production of IL-1beta, a cytokine implicated in a variety of inflammatory diseases, requires cleavage of its precursor (proIL-1beta) at an Asp-X site by interleukin-1beta-converting enzyme (ICE, recently termed caspase-1). The Asp-X sequence at the putative processing site in proIGIF suggests that a protease such as caspase-1 might be involved in the maturation of IGIF. Here we demonstrate that caspase-1 processes proIGIF and proIL-1beta with equivalent efficiencies in vitro. A selective caspase-1 inhibitor blocks both lipopolysaccharide-induced IL-1beta and IFN-gamma production from human mononuclear cells. Furthermore, caspase-1-deficient mice are defective in lipopolysaccharide-induced IFN-gamma production. Our results thus implicate caspase-1 in the physiological production of IGIF and demonstrate that it plays a critical role in the regulation of multiple proinflammatory cytokines. Specific caspase-1 inhibitors would provide a new class of anti-inflammatory drugs with multipotent action.

PubMed Disclaimer

Similar articles

Cited by

MeSH terms

Substances

LinkOut - more resources