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IKBKB — PTGS2
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Chen et al., Mol Pharmacol 2001
:
TNF-alpha- or C2-ceramide induced
COX-2 promoter activity was
inhibited by the dominant negative mutant of extracellular signal regulated kinase 2, p38, JNK,
IkappaB kinase (IKK)1 , or IKK2
Nakatani et al., Mol Pharmacol 2004
(Brain Neoplasms...) :
These results suggest that gamma-mangostin directly inhibits
IKK activity and thereby
prevents COX-2 gene transcription, an NF-kappaB target gene, probably to decrease the inflammatory agent stimulated PGE ( 2 ) production in vivo, and is a new useful lead compound for anti-inflammatory drug development
Chang et al., Mol Pharmacol 2004
:
The dominant negative mutants of NIK and various
IkappaB kinase complexes, including IKKbeta ( Y188F ), IKKbeta ( Y199F ), and IKKbeta ( FF ),
inhibited the
COX-2 promoter activity
Joo et al., J Virol 2005
:
NF-kappaB activation by either LPS or overexpression of
IKKbeta was
sufficient to induce robust expression of
COX-2 , which was markedly suppressed by ectopic expression of HCV core
Kundu et al., Carcinogenesis 2006
:
Topical application of Bay 11-7082 also abrogated TPA induced NF-kappaB activation and COX-2 expression, supporting the
involvement of
IKK in TPA induced
COX-2 expression
Pan et al., Biochem Pharmacol 2006
(Cocarcinogenesis...) :
Taken together, these results show that acacetin down
regulates inflammatory iNOS and
COX-2 gene expression in macrophages by inhibiting the activation of NF kappa B by interfering with the activation
PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation associated tumorigenesis
Hwang et al., Carcinogenesis 2007
:
Taken together, 9Z,11E-CLA
inhibits NF-kappaB
driven-COX-2 expression by blocking the
IKK and PI3K-Akt signaling in TPA treated hairless mouse skin in vivo, which may account for its previously reported anti-tumor promoting effects
Ding et al., J Biol Chem 2006
:
Overexpression of
IKKbeta-KM , a kinase inactive mutant of IKKbeta,
blocked NF-kappaB activation and
COX-2 induction by nickel compounds, indicating that activated NF-kappaB may be a mediator for COX-2 induction ... Loss of
IKKbeta impaired
COX-2 induction by nickel exposure, whereas knockout of IKKalpha had a marginal effect
Polk et al., Am J Physiol Cell Physiol 2007
(Nephritis) :
RhoA regulation of NF-kappaB activation is mediated by
COX-2 dependent feedback inhibition of
IKK in kidney epithelial cells ... Moreover, inhibition of
COX-2 activity
results in persistent p65-DNA binding, IkappaBalpha phosphorylation, and
IKKbeta activity, similar to that observed after prevention of RhoA/AP-1 axis signaling
Ding et al., Cancer Sci 2007
:
The
IKKbeta/NF-kappaB dependent
COX-2 induction was further confirmed in mouse embryonic fibroblasts with IKKbeta deficiency ( IKKbeta ( -/- ) ) and in those that expressed reconstituted IKKbeta
Pan et al., J Agric Food Chem 2008
:
Taken together, these results show that pterostilbene down
regulates inflammatory iNOS and
COX-2 gene expression in macrophages by inhibiting the activation of NFkappaB by interfering with the activation of
PI3K/Akt/IKK and MAPK
Shih et al., Eur J Pharmacol 2009
:
In this study, we investigated the
involvement of the extracellular signal regulated kinase ( ERK ),
IkappaB kinase alpha/beta ( IKKalpha/beta ), and nuclear factor-kappaB (NF-kappaB) signaling pathways in thrombin induced
COX-2 expression in human lung fibroblasts ( WI-38 )
Zhang et al., Inflammation 2010
(Inflammation) :
These results suggest that resistin enhances
COX-2 expression in mouse macrophage cells in a
TAK1-IKK-NF-kappaB dependent manner and therefore plays a critical role in inflammatory processes
Kumar et al., Carcinogenesis 2012
(Carcinoma, Squamous Cell...) :
Single application of NX ( 1.0mg/mouse ) prior to 12-O-tetradecanoylphorbol 13-acetate ( TPA ) application significantly inhibited TPA induced skin edema, hyperplasia, thymidine incorporation and ornithine decarboxylase (ODC) activity ; expression of
cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) ; phosphorylation of extracellular signal regulated kinases ( ERK ) 1/2, p38 and c-jun N-terminal kinase ( JNK ) mitogen activated protein kinases ( MAPKs ) ; and
activation of
I kappa B kinase (IKK) , I?Ba and nuclear factor-kappa B ( NF-?B ) in mouse skin