Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperoxia and tumor necrosis factor-alpha (TNFalpha) are two canonical signals centrally involved in the pathophysiology of acute lung injury. We have attempted to elucidate the effects of these two stimuli on the signal transduction pathways of lung parenchymal cells. In cultured human lung epithelial cells, exposure to hyperoxia alone (95% oxygen) did not affect NF-kappaB activation or degradation of the NF-kappaB inhibitory protein, IkappaB alpha. Stimulation with TNFalpha alone increased NF-kappaB activation within 1 h and induced IkappaB alpha degradation within 0.5 h. After TNFalpha alone, NF-kappaB activation returned to baseline within 2 h and this corresponded with near complete IkappaB alpha resynthesis within 1 h of stimulation. In contrast, simultaneous exposure to hyperoxia and TNFalpha prolonged NF-kappaB activation up to 4 h, and IkappaB alpha degradation up to 2 h after stimulation. Hyperoxia did not affect TNFalpha-mediated resynthesis of IkappaB alpha mRNA. Hyperoxia alone did not induce IkappaB kinase (IKK) activity, but significantly prolonged TNFalpha-mediated activation of IKK activity. Hyperoxia alone did not activate the intercellular adhesion molecule-1 (ICAM-1) promoter, but augmented TNFalpha-mediated activation of the ICAM-1 promoter. These data demonstrate that while hyperoxia alone does not affect activation of NF-kappaB, hyperoxia prolongs TNFalpha-mediated activation of NF-kappaB. The mechanism of this effect involves, in part, prolonged degradation of IkappaB alpha resulting from prolonged activation of IKK.
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PMID:Hyperoxia prolongs tumor necrosis factor-alpha-mediated activation of NF-kappaB: role of IkappaB kinase. 1195 26

We have been interested in elucidating how simultaneous stimuli modulate inflammation-related signal transduction pathways in lung parenchymal cells. We previously demonstrated that exposing respiratory epithelial cells to 95% oxygen (hyperoxia) synergistically increased tumor necrosis factor-alpha (TNF-alpha)-mediated activation of NF-kappaB and NF-kappaB-dependent gene expression by a mechanism involving increased activation of IkappaB kinase (IKK). Because the signal transduction mechanisms induced by IL-1beta are distinct to that of TNF-alpha, herein we sought to determine whether hyperoxia modulates IL-1beta-dependent signal transduction. In A549 cells, simultaneous treatment with hyperoxia and IL-1beta caused increased activation of IKK, prolonged the degradation of IkappaBalpha, and prolonged the nuclear translocation and DNA binding of NF-kappaB compared with cells treated with IL-1beta alone in room air. Hyperoxia did not affect IL-1beta-dependent degradation of the interleukin receptor-associated kinase differently from treatment with IL-beta alone. In contrast to the effects on the IKK/IkappaBalpha/NF-kappaB pathway, simultaneous treatment with hyperoxia and IL-1beta did not augment NF-kappaB-dependent gene expression compared with treatment with IL-1beta alone. Similar observations were made in a different human respiratory epithelial cell line, BEAS-2B cells. In addition, simultaneous treatment with hyperoxia and IL-1beta caused hyperphosphorlyation of the NF-kappaB p65 subunit compared with treatment with IL-1beta alone. In summary, concomitant treatment of A549 cells with hyperoxia and IL-1beta augments activation of IKK, prolongs degradation of IkappaBalpha, and prolongs nuclear translocation and DNA binding of NF-kappaB. This activation, however, is not coupled to increased expression of NF-kappaB-dependent genes, and the mechanism of this decoupling is not related to decreased phosphorylation of p65.
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PMID:Short-term modulation of interleukin-1beta signaling by hyperoxia: uncoupling of IkappaB kinase activation and NF-kappaB-dependent gene expression. 1461 15