Acute alcohol inhibits the induction of nuclear regulatory factor kappa B activation through CD14/toll-like receptor 4, interleukin-1, and tumor necrosis factor receptors: a common mechanism independent of inhibitory kappa B alpha degradation

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dc.contributor.authorMandrekar, Pranoti
dc.contributor.authorDolganiuc, Angela
dc.contributor.authorBellerose, Gary
dc.contributor.authorKodys, Karen
dc.contributor.authorRomics, Laszlo
dc.contributor.authorNizamani, Rabia
dc.contributor.authorSzabo, Gyongyi
dc.contributor.departmentDepartment of Medicine, Rheumatology Division
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.date2022-08-11T08:08:37.000
dc.date.accessioned2022-08-23T16:01:23Z
dc.date.available2022-08-23T16:01:23Z
dc.date.issued2002-11-19
dc.date.submitted2010-04-21
dc.description.abstractBACKGROUND: Nuclear translocation and DNA binding of the nuclear factor kappaB (NF-kappaB) is an early event in inflammatory cell activation in response to stimulation with bacterial components or cytokines. Cell activation via different receptors culminates in a common pathway leading to NF-kappaB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-kappaB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-kappaB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. METHODS: Human peripheral blood monocytes were treated with LPS, TNFalpha, and IL-1beta in the presence or absence of 25mM alcohol for 1 hr. NF-kappaB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory kappaB(alpha) (IkappaB(alpha)) was estimated by Western blotting in cytoplasmic extracts. Chinese hamster ovary cells expressing human CD14 were treated with LPS in the presence or absence of alcohol to study NF-kappaB and IkappaB(alpha) regulation. RESULTS: Our results indicate that acute alcohol inhibits IL-1beta- and TNFalpha-induced NF-kappaB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-kappaB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-kappaB by acute alcohol was concomitant with decreased levels of the IkappaB(alpha) molecule in the cytoplasm of LPS, IL-1, and TNFalpha-activated monocytes. CONCLUSIONS: These data suggest a unique, IkappaB(alpha)-independent pathway for the inhibition of NF-kappaB activation by acute alcohol in monocytes. Universal inhibition of NF-kappaB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-kappaB activation cascade that is downstream from IkappaB(alpha) degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-kappaB activation by mediators of early (LPS) or late (IL-1, TNF(alpha)) stages of inflammation in monocytes.
dc.identifier.citationAlcohol Clin Exp Res. 2002 Nov;26(11):1609-14. <a href="http://dx.doi.org/10.1097/01.ALC.0000036926.46632.57">Link to article on publisher's site</a>
dc.identifier.contextkey1282331
dc.identifier.doi10.1097/01.ALC.0000036926.46632.57
dc.identifier.issn0145-6008 (Linking)
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gastroenterology_pp/36
dc.identifier.pmid12436048
dc.identifier.submissionpathgastroenterology_pp/36
dc.identifier.urihttps://hdl.handle.net/20.500.14038/31110
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12436048&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1111/j.1530-0277.2002.tb02462.x
dc.source.issue11
dc.source.journaltitleAlcoholism, clinical and experimental research
dc.source.pages1609-14
dc.source.volume26
dc.subjectAnimals
dc.subjectAntigens, CD14
dc.subjectCHO Cells
dc.subjectCricetinae
dc.subject*Drosophila Proteins
dc.subjectEthanol
dc.subjectHumans
dc.subjectI-kappa B Proteins
dc.subjectLeukocytes, Mononuclear
dc.subjectMembrane Glycoproteins
dc.subjectNF-kappa B
dc.subjectReceptors, Cell Surface
dc.subjectReceptors, Interleukin-1
dc.subjectReceptors, Tumor Necrosis Factor
dc.subjectToll-Like Receptor 4
dc.subjectToll-Like Receptors
dc.subjectGastroenterology
dc.subjectImmunology and Infectious Disease
dc.titleAcute alcohol inhibits the induction of nuclear regulatory factor kappa B activation through CD14/toll-like receptor 4, interleukin-1, and tumor necrosis factor receptors: a common mechanism independent of inhibitory kappa B alpha degradation
dc.typeJournal Article
dspace.entity.typePublication
html.description.abstract<p>BACKGROUND: Nuclear translocation and DNA binding of the nuclear factor kappaB (NF-kappaB) is an early event in inflammatory cell activation in response to stimulation with bacterial components or cytokines. Cell activation via different receptors culminates in a common pathway leading to NF-kappaB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-kappaB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-kappaB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors.</p> <p>METHODS: Human peripheral blood monocytes were treated with LPS, TNFalpha, and IL-1beta in the presence or absence of 25mM alcohol for 1 hr. NF-kappaB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory kappaB(alpha) (IkappaB(alpha)) was estimated by Western blotting in cytoplasmic extracts. Chinese hamster ovary cells expressing human CD14 were treated with LPS in the presence or absence of alcohol to study NF-kappaB and IkappaB(alpha) regulation.</p> <p>RESULTS: Our results indicate that acute alcohol inhibits IL-1beta- and TNFalpha-induced NF-kappaB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-kappaB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-kappaB by acute alcohol was concomitant with decreased levels of the IkappaB(alpha) molecule in the cytoplasm of LPS, IL-1, and TNFalpha-activated monocytes.</p> <p>CONCLUSIONS: These data suggest a unique, IkappaB(alpha)-independent pathway for the inhibition of NF-kappaB activation by acute alcohol in monocytes. Universal inhibition of NF-kappaB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-kappaB activation cascade that is downstream from IkappaB(alpha) degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-kappaB activation by mediators of early (LPS) or late (IL-1, TNF(alpha)) stages of inflammation in monocytes.</p>
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