Mice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock

We report here results with IL-lp-converting enzyme -deficient mice

Ping Li; Hamish Allen; Subhashis Banerjee; Simon Franklin; Linda Herzog; Cynthia Johnston; Jack McDowell; Michael Paskind; Laura Rodman; Jochen Salfeld; Elizabeth Towne; Daniel Tracey; Scott Wardwell; Feng-Yi Wei; Winnie Wong; Robert Kamen; Tara Seshadri

2004

Scholarcy highlights

  • Interleukin-ll~-converting enzyme is the cysteine protease that generates the bioactive form of the proinflammatory cytokine IL-113from its biologically inactive precursor
  • We report here results with IL-lp-converting enzyme-deficient mice
  • ICE-Deficient Mice Survive LPS-lnduced Septic Shock and Produce No Detectable IL-lJ~ or IL-la In Vivo Injection of high doses of LPS intraperitoneally into mice induces the massive systemic release of proinflammatory cytokines such as both types of IL-1 and TNFm These cytokines are important in the pathogenesis of systemic inflammatory response syndrome and septic shock, which develops in the animals and results in their death
  • The small amount of mature IL-113released by the macrophages from mutant mice was of the correct molecular weight, suggesting that specific cleavage of pro-lL-113may occur in the mutant cells, at a very low level
  • Macrophages from mice heterozygous for the ICE mutation produced about half the mature IL-113level of those from wild-type mice, implying that the rate of IL-113release from cells is proportional to ICE gene dosage
  • There were no significant differences in the CD4+CD8÷, CD4+CD8, CD4-CD8÷, CD4-CD8, and B cell populations in any of these organs as compared with those of wild-type animals
  • Using the methods described in the kits and the dilutions used for the assays, we found the detection limits for IL-I~, and IL-l~ to be 20 pg/ml and 30 pg/ml, respectively
  • IL-lp-converting enzyme plays a dominant role in the generation of mature IL-11], a previously unsuspected role in production of IL-le, but has no autonomous function in apoptosis

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