+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

IL-12-induced IFN-gamma is dependent on caspase-1 processing of the IL-18 precursor



IL-12-induced IFN-gamma is dependent on caspase-1 processing of the IL-18 precursor



Journal of Clinical Investigation 104(6): 761-767



IL-12 and IL-18 are IFN-gamma-inducing cytokines. In the present study, the role of endogenous IL-18 in the induction of IFN-gamma by IL-12 was investigated in mice. In the presence of a specific inhibitor of caspase-1 (also known as IL-1beta-converting enzyme, or ICE) IL-12-induced IFN-gamma from splenocytes was reduced by 85%. Using splenocytes from ICE-deficient mice, IL-12-induced IFN-gamma was reduced by 80%. However, the role of ICE was not through processing and release of IL-1beta. Neutralizing anti-IL-18 IgG reduced IL-12-induced IFN-gamma in splenocytes by 85%. Splenocytes cultured in vitro spontaneously released IL-18 into the extracellular compartment over time. Extracellular levels of IL-18 significantly correlated with IL-12-induced IFN-gamma and were reduced in cells obtained from ICE-deficient mice. In vivo, IL-12 administration increased circulating levels of IL-18 in wild-type mice but not in ICE-deficient mice. Both neutralization of IL-18 and ICE deficiency significantly reduced induction of circulating IFN-gamma in mice receiving IL-12. The IL-18 precursor was constitutively expressed in the livers and spleens of untreated mice. Furthermore, administration of IL-12 significantly increased liver-associated IL-18 levels. These data demonstrate that endogenous, ICE-cleaved IL-18 significantly contributes to induction of IFN-gamma by IL-12.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 010777286

Download citation: RISBibTeXText

PMID: 10491411


Related references

Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3. Journal of Biological Chemistry 276(24): 21907-21915, 2001

Bcl-xL, caspase-3 and caspase-8 regulation of interferon-gamma-induced apoptosis through Fas-dependent and Fas-independent pathways in human B lymphoma SKW6.4 cells. International Journal of Immunotherapy 18(2): 31-43, 2002

Switch from caspase-dependent to caspase-independent death during heart development: essential role of endonuclease G in ischemia-induced DNA processing of differentiated cardiomyocytes. Journal of Biological Chemistry 281(32): 22943-22952, 2006

Interferon-gamma-induced apoptosis in Fanconi anemia group C hematopoietic progenitor cells involves caspase-8-dependent activation of caspase 3 family members. Blood 94(10 Suppl. 1 Part 1): 408a, 1999

Interferon-gamma-induced apoptotic responses of Fanconi anemia group C hematopoietic progenitor cells involve caspase 8-dependent activation of caspase 3 family members. Blood 96(13): 4204-4211, 2000

Genotoxin-induced neural precursor cell apoptosis is p53- and caspase-9-dependent. Society for Neuroscience Abstracts 26(1-2): Abstract No -227 16, 2000

3T3-L1 adipocyte apoptosis induced by thiazolidinediones is peroxisome proliferator-activated receptor-gamma-dependent and mediated by the caspase-3-dependent apoptotic pathway. Febs Journal 277(3): 687-696, 2010

Fe65 is not involved in the platelet-derived growth factor-induced processing of Alzheimer's amyloid precursor protein, which activates its caspase-directed cleavage. Journal of Biological Chemistry 279(16): 16161-9, 2004

Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. Embo Reports 2(9): 835-841, 2001

Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression. Proceedings of the National Academy of Sciences of the United States of America 104(25): 10613-8, 2007

Phosphorylation of amyloid precursor carboxy-terminal fragments enhances their processing by a gamma-secretase-dependent mechanism. Neurobiology of Disease 20(2): 625-637, 2005

DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3. Development 128(1): 137-146, 2001

Caspase-12 and caspase-4 are not required for caspase-dependent endoplasmic reticulum stress-induced apoptosis. Journal of Biological Chemistry 280(33): 29578-29587, 2005

IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1. Intensive Care Medicine Experimental 1(1): 27, 2013

Death receptor-induced signaling pathways are differentially regulated by gamma interferon upstream of caspase 8 processing. Molecular and Cellular Biology 25(15): 6363-6379, 2005