Acute alcohol inhibits the induction of nuclear regulatory factor κB activation through CD14/Toll- like receptor 4, interleukin-1, and tumor necrosis factor receptors: A common mechanism independent of inhibitory κbα degradation?

Pranoti Mandrekar, Angela Dolganiuc, Gary Bellerose, Karen Kodys, Laszlo Romics, Rabia Nizamani, G. Szabó

Research output: Contribution to journalArticle

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Abstract

Background: Nuclear translocation and DNA binding of the nuclear factor κB (NF-κB) 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-κB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-κB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-κB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. Methods: Human peripheral blood monocytes were treated with LPS, TNFα, and IL-1β in the presence or absence of 25mM alcohol for 1 hr. NF-κB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory κBα (IκBα) 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-κB and IκBα regulation. Results: Our results indicate that acute alcohol inhibits IL-1β- and TNFα-induced NF-κB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-κB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-κB by acute alcohol was concomitant with decreased levels of the IκBα molecule in the cytoplasm of LPS, IL-1, and TNFα-activated monocytes. Conclusions: These data suggest a unique, IκBα-independent pathway for the inhibition of NF-κB activation by acute alcohol in monocytes. Universal inhibition of NF-κB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-κB activation cascade that is downstream from IκBα degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-κB activation by mediators of early (LPS) or late (IL-1, TNFα) stages of inflammation in monocytes.

Original languageEnglish
Pages (from-to)1609-1614
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume26
Issue number11
Publication statusPublished - Nov 1 2002

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Toll-Like Receptor 4
Tumor Necrosis Factor Receptors
Interleukin-1
Chemical activation
Alcohols
Degradation
Monocytes
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Cricetulus
Ovary
Cells
Cytokines
Electrophoretic mobility
Electrophoretic Mobility Shift Assay
Assays
Cytoplasm
Blood
Western Blotting
Inflammation

Keywords

  • Ethanol
  • Inflammation
  • Macrophages
  • Monocyte

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Acute alcohol inhibits the induction of nuclear regulatory factor κB activation through CD14/Toll- like receptor 4, interleukin-1, and tumor necrosis factor receptors : A common mechanism independent of inhibitory κbα degradation? / Mandrekar, Pranoti; Dolganiuc, Angela; Bellerose, Gary; Kodys, Karen; Romics, Laszlo; Nizamani, Rabia; Szabó, G.

In: Alcoholism: Clinical and Experimental Research, Vol. 26, No. 11, 01.11.2002, p. 1609-1614.

Research output: Contribution to journalArticle

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title = "Acute alcohol inhibits the induction of nuclear regulatory factor κB activation through CD14/Toll- like receptor 4, interleukin-1, and tumor necrosis factor receptors: A common mechanism independent of inhibitory κbα degradation?",
abstract = "Background: Nuclear translocation and DNA binding of the nuclear factor κB (NF-κB) 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-κB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-κB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-κB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. Methods: Human peripheral blood monocytes were treated with LPS, TNFα, and IL-1β in the presence or absence of 25mM alcohol for 1 hr. NF-κB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory κBα (IκBα) 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-κB and IκBα regulation. Results: Our results indicate that acute alcohol inhibits IL-1β- and TNFα-induced NF-κB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-κB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-κB by acute alcohol was concomitant with decreased levels of the IκBα molecule in the cytoplasm of LPS, IL-1, and TNFα-activated monocytes. Conclusions: These data suggest a unique, IκBα-independent pathway for the inhibition of NF-κB activation by acute alcohol in monocytes. Universal inhibition of NF-κB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-κB activation cascade that is downstream from IκBα degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-κB activation by mediators of early (LPS) or late (IL-1, TNFα) stages of inflammation in monocytes.",
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T1 - Acute alcohol inhibits the induction of nuclear regulatory factor κB activation through CD14/Toll- like receptor 4, interleukin-1, and tumor necrosis factor receptors

T2 - A common mechanism independent of inhibitory κbα degradation?

AU - Mandrekar, Pranoti

AU - Dolganiuc, Angela

AU - Bellerose, Gary

AU - Kodys, Karen

AU - Romics, Laszlo

AU - Nizamani, Rabia

AU - Szabó, G.

PY - 2002/11/1

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N2 - Background: Nuclear translocation and DNA binding of the nuclear factor κB (NF-κB) 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-κB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-κB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-κB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. Methods: Human peripheral blood monocytes were treated with LPS, TNFα, and IL-1β in the presence or absence of 25mM alcohol for 1 hr. NF-κB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory κBα (IκBα) 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-κB and IκBα regulation. Results: Our results indicate that acute alcohol inhibits IL-1β- and TNFα-induced NF-κB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-κB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-κB by acute alcohol was concomitant with decreased levels of the IκBα molecule in the cytoplasm of LPS, IL-1, and TNFα-activated monocytes. Conclusions: These data suggest a unique, IκBα-independent pathway for the inhibition of NF-κB activation by acute alcohol in monocytes. Universal inhibition of NF-κB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-κB activation cascade that is downstream from IκBα degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-κB activation by mediators of early (LPS) or late (IL-1, TNFα) stages of inflammation in monocytes.

AB - Background: Nuclear translocation and DNA binding of the nuclear factor κB (NF-κB) 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-κB activation and proinflammatory cytokine induction. We have previously shown that acute alcohol inhibits NF-κB activation by lipopolysaccharide (LPS) in human monocytes. Here we investigated whether acute alcohol treatment of human monocytes also inhibits NF-κB when induced through activation of the interleukin (IL)-1 or tumor necrosis factor (TNF) receptors. Methods: Human peripheral blood monocytes were treated with LPS, TNFα, and IL-1β in the presence or absence of 25mM alcohol for 1 hr. NF-κB activation was determined by electrophoretic mobility shift assays using nuclear extracts. Inhibitory κBα (IκBα) 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-κB and IκBα regulation. Results: Our results indicate that acute alcohol inhibits IL-1β- and TNFα-induced NF-κB activation. We further show in CD14/toll-like receptor 4-expressing Chinese hamster ovary cells the specificity of alcohol-mediated inhibition of NF-κB via the toll-like receptor 4/CD14 receptors. Inhibition of NF-κB by acute alcohol was concomitant with decreased levels of the IκBα molecule in the cytoplasm of LPS, IL-1, and TNFα-activated monocytes. Conclusions: These data suggest a unique, IκBα-independent pathway for the inhibition of NF-κB activation by acute alcohol in monocytes. Universal inhibition of NF-κB by acute alcohol via these various receptor systems suggests a target for the effects of alcohol in the NF-κB activation cascade that is downstream from IκBα degradation. Further, these results demonstrate that acute alcohol is a potent inhibitor of NF-κB activation by mediators of early (LPS) or late (IL-1, TNFα) stages of inflammation in monocytes.

KW - Ethanol

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KW - Macrophages

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