title: Anti-inflammatory effect of heat shock protein induction is related to stabilization of I kappa B alpha through preventing I kappa B kinase activation in respiratory epithelial cells.
abstract: Heat shock protein (HSP) induction confers protection against diverse forms of cellular and tissue injury. However, the mechanism by which HSP exerts cytoprotective effects is unclear. Because HSP induction inhibits genetic expression of pro-inflammatory cytokines, the transcription of which is dependent on NF-kappa B activation, we explored the relationship between the anti-inflammatory effect of HSP induction and the NF-kappa B/I kappa B alpha pathway. Both HS and sodium arsenite treatment increased HSP70 expression time dependently at mRNA and protein levels. Prior induction of HSP suppressed cytokine-induced IL-8 and TNF-alpha expression at both mRNA and protein levels. Although HSP induction did not affect total cellular expression of NF-kappa B, TNF-alpha-induced increase in NF-kappa B-DNA binding activity and nuclear translocation of the p65 subunit of NF-kappa B were inhibited by prior HSP induction, suggesting that activation of NF-kappa B was blocked. Cytokine-induced I kappa B alpha phosphorylation and its degradation were blocked in HSP-induced cells. Immune complex kinase assays demonstrated that TNF-alpha induced increase in I kappa B kinase activity was suppressed by prior HSP induction. These results suggest that the anti-inflammatory effect of HSP induction in respiratory epithelial cells is related to stabilization of I kappa B alpha, possibly through the prevention of I kappa B kinase activation, which thereby inhibits activation of NF-kappa B.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. cgyoo@snu.ac.kr
authors.forename: C G
authors.initials: CG
authors.lastname: Yoo
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: C T
authors.initials: CT
authors.lastname: Lee
authors.forename: Y W
authors.initials: YW
authors.lastname: Kim
authors.forename: S K
authors.initials: SK
authors.lastname: Han
authors.forename: Y S
authors.initials: YS
authors.lastname: Shim
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D017670:Sodium Compounds / Q000494:pharmacology; D013997:Time Factors; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018053:Arsenites; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D020672:I-kappa B Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D017670:Sodium Compounds; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C017947:sodium arsenite; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human