Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.10 (IKK)
 4,900 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular ATP, acting at P2Y and P2X receptors, has recently been shown to contribute to airway inflammation. The aim of our study was to investigate the molecular mechanisms involved in the ATP-dependent regulation of IL-8 production by airway epithelial cells. Treatment of human normal tracheal (NT)-1 cells with ATP or its two analogs, alpha,beta-methylene ATP (alpha,beta-meATP) and 2'- and 3'-O-(4-benzoyl-benzoyl)-ATP (BzATP) activated NF-kappaB through the IkappaB kinase (IKK) complex, a process requiring Ca(2+), calmodulin (CaM), and Ca(2+)/CaM-dependent kinase (CaMK), but independent from phospholipase C. alpha,beta-meATP-induced IKK activation also occurred in the alveolar A549 cell line. Real-time RT-PCR revealed that NT-1 and A549 cells expressed P2X(4), P2X(5),and P2X(6) subtype mRNAs, whereas P2X(7) mRNAs were only detected in NT-1 cells. Polarized human primary nasal epithelial cells expressed all four P2X subtypes. Both alpha,beta-meATP and BzATP caused Ca(2+)-dependent binding of phosphorylated p65 (S536) NF-kappaB subunit to the endogenous IL-8 gene promoter in NT-1 cells. Although these agonists did not induce significant IL-8 gene expression by these cells, they markedly enhanced TNF-alpha-induced NF-kappaB activation, resulting in increased IL-8 expression and release. Application of alpha,beta-meATP or BzATP at the apical side of polarized human primary nasal epithelial cells sufficed to cause CaMK-dependent IL-8 release by these cells. Thus, ATP promotes TNF-alpha-elicited IL-8 expression through P2X ion channel-triggered Ca(2+) entry, leading to CaMK-dependent IKK activation and binding of active p65 to IL-8 gene promoter.
 ...
PMID:A P2X ion channel-triggered NF-kappaB pathway enhances TNF-alpha-induced IL-8 expression in airway epithelial cells. 3300 Sep 73