Response to local inflammation of IL-1 beta-converting enzyme- deficient mice.
IL-1 beta-converting enzyme (ICE) cleaves pro-IL-1 beta to the mature, released form. Although other proteases can process pro-IL-1 beta, ICE-deficient (ICE -/-) mice do not release mature IL-1 beta in response to endotoxin. The purpose of our study was to investigate the response of ICE -/- mice in two models of local inflammation, turpentine-induced tissue damage and zymosan-induced peritonitis. No differences were observed in the development of the systemic acute phase response after turpentine administration between wild-type and ICE -/- mice, but this response was completely impaired in IL-1 beta -/- mice. Accordingly, the levels of mature IL-1 beta produced in response to turpentine did not differ between wild-type and ICE -/- mice. In contrast, following zymosan-induced peritonitis, the levels of mature IL-1 beta were significantly lower in ICE -/- mice. This was associated with a 50% decrease in cellular infiltrate in ICE -/- mice compared with that in wild-type controls. The reduced production of zymosan-induced mature IL-1 beta in ICE -/- mice was also observed from cultured peritoneal or spleen cells. Our results demonstrate that in turpentine-induced tissue necrosis, precursor IL-1 beta is processed by non-ICE proteases, but in complement-mediated inflammation, ICE participates in the processing of the IL-1 beta precursor.
Fantuzzi
G
G
Department of Medicine, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111, USA.
Ku
G
G
Harding
M W
MW
Livingston
D J
DJ
Sipe
J D
JD
Kuida
K
K
Flavell
R A
RA
Dinarello
C A
CA
D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis; D001835:Body Weight / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D020170:Caspase 1; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000172:deficiency* / Q000235:genetics*; D016207:Cytokines / Q000097:blood; D007249:Inflammation / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency; D051379:Mice; D008817:Mice, Mutant Strains; D000685:Serum Amyloid A Protein / Q000096:biosynthesis; D014425:Turpentine / Q000008:administration & dosage; D015054:Zymosan / Q000008:administration & dosage / Q000494:pharmacology
D001053:Apolipoproteins; D016207:Cytokines; D007375:Interleukin-1; D000685:Serum Amyloid A Protein; D015054:Zymosan; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D014425:Turpentine