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PMID: 10807517, 9427712 LPS has been reported to have the capacity to induce the activation of caspase-1.

PMID: 10807517, 9034139, 9388494 Enzyme activities of some caspases including caspase-1 are reversibly downregulated by nitric oxide (NO), via direct S-nitrosylation of caspase catalytic cysteine residues . Downmodulation of caspase-1 by NO results in reduction of IL-1 and IL-18 secretion from LPS-activated macrophages (59), suggesting a possible negative feedback of IL-18 production by NO.

PMID: 10807517 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8

PMID: 10807517, 10514014 caspase-1-deficient mice secreted biologically active IL-18 after stimulation with membrane-associated FasL or soluble FasL

PMID: 10807517, 9521326, 8681377 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8

PMID: 10807517 IL-18 BP prevents mature IL-18 from binding to its authentic receptor IL-18R,

PMID: 10807517 IL-18 BP has the capacity to bind to IL-18 without exhibiting species specificity.

PMID: 10807517, 10227969, 9759857, 10653850 When IL-18R or IL-1R is activated by corresponding ligand, MyD88 is recruited to the intracellular domain of each receptor.

PMID: 10807517 After activation with IL-18, IL-18R recruits MyD88, an adapter protein, providing a platform for the IL-1R associated kinase (IRAK).

PMID: 10807517, 9354477, 9177292, 9514903 IL-18R shares a signal transducing pathway with IL-1R

PMID: 10807517 After activation with IL-18, IL-18R recruits MyD88, an adapter protein, providing a platform for the IL-1R associated kinase (IRAK).

PMID: 10807517 IRAK subsequently undergoes phosphorylation.

PMID: 10807517 IRAK subsequently undergoes phosphorylation and interacts with the TNFR-associated factor (TRAF) 6.

PMID: 10807517 IRAK subsequently undergoes phosphorylation and interacts with the TNFR-associated factor (TRAF) 6, leading to nuclear translocation of NFkappaB.

PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK) and NFkappaB.

Indirect

PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK)

PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4.

PMID: 10807517 Murine IL-18 is produced as a biologically inactive precursor of 24 kDa (proIL-18), and proIL-18 is cleaved into biologically active mature IL-18 of 18 kDa by caspase-1, originally designated as IL-1-converting enzyme (ICE).

Indirect

PMID: 10807517 First, mRNA forIL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge. Second,the hepatic IFN-gamma mRNA level is enhanced soon after the elevation of IL-12 p40.

Indirect

PMID: 10807517, 11513148 mRNA for IL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge.

PMID: 10807517, 10500213, 10201887, 10549626, 9751057, 9841923, 10426996 LPS is recognized by TLR-4 in mouse and TLR-2 in human.

Indirect

PMID: 10807517, 9354477, 9177292, 9514903 IL-18 does not activate the JAK/STAT system, but activates the IRAK/TRAF6 pathway resulting in the activation of both activator protein (AP)-1 (via JNK) and NFkappaB.

Indirect

PMID: 10807517 LPS challenge seems to induce rapid secretion of both IL-18 and IL-12 from Kupffer cells, which cause hepatic lymphocytes to produce a huge amount of IFN- gamma, leading to the second elevation of TNF-alpha.

Indirect

PMID: 10807517 After LPS challenge, IL-18 is secreted from Kupffer cells, which initiates the ordered action of IFN-alpha and TNF-alpha.

Indirect

PMID: 10807517 IL-18 accumulated in the liver also induces FasL expression on hepatic effector cells

Indirect

PMID: 10807517 IL-18 gene expression may be upregulated by the direct stimulation with microbial products such as LPS

PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4, a member of the STAT family,which induces the activation of IFN-gamma gene expression through binding of STAT4 to the corresponding binding site in the IFN-gamma promoter region.

PMID: 10807517 The activation of Fas recruits an adaptor molecule, Fas-associated death domain protein, which binds to and activates caspase-8

PMID: 10807517, 9491891 Precursor caspase-1 is cleaved into its mature form by caspase-11 or autoproteolytically.

PMID: 10807517, 8670419, 7722452 IL-12 activates STAT4, a member of the STAT family, which induces the activation of IFN-gamma gene expression

PMID: 10807517, 10500213, 10201887, 10549626, 9751057, 9841923, 10426996 LPS is recognized by TLR-4 in mouse and TLR-2 in human.

PMID: 10807517, 11513148 mRNA for IL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge.

PMID: 10807517 IL-18 gene expression may be upregulated by the direct stimulation with microbial products such as LPS

PMID: 10807517 First, mRNA forIL-12 p40, an inducible component of the biologically active IL-12 heterodimer, is elevated in the liver after LPS challenge. Second,the hepatic IFN-gamma mRNA level is enhanced soon after the elevation of IL-12 p40.

PMID: 10807517 After LPS challenge, IL-18 is secreted from Kupffer cells, which initiates the ordered action of IFN-alpha and TNF-alpha.

PMID: 10807517, 10227969, 9759857, 10653850 When IL-18R or IL-1R is activated by corresponding ligand, MyD88 is recruited to the intracellular domain of each receptor.

PMID: 10807517, 8999548 Caspase-4 has the capacity to cleave proIL-18 after the 35Asp residue, the same site at which caspase-1 does. However, the efficiency of IL-18 processing by caspase-4 is one hundredth or one thousandth that of caspase-1 (26).

PMID: 10807517, 8999548, 9334240 Caspase-3 can also cleave IL-18, but at a different site, 69Asp-70Ile, resulting in the accumulation of biologically inactive products (26, 61).

PMID: 10807517, 8706881, 9463409, 10235259, 9917913 The activated caspase-8 then sequentially activates downstream caspases, such as caspase-3, 6 and 7 (67–70).