title: Heat effect induces production of inflammatory cytokines through heat shock protein 90 pathway in cornea cells.
abstract: OBJECTIVE
  Many studies have been conducted to elucidate the molecular consequences of ultraviolet irradiation, whereas little is known about the effect of infrared radiation on ocular disease. Heat is generated as a consequence of infrared irradiation, in addition to photons, and heat shock is widely considered to be an environmental stressor. Our previous study has demonstrated that heat shock (42 °C) induces apoptosis of Statens Seruminstitut Rabbit Cornea (SIRC) cells. However, the biological effect of mild heat shock (39 °C), which does not induce apoptosis, on SIRC cells has not been studied yet.
  
  
  METHODS
  The SIRC cells were treated with mild heat shock and the expression of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6), in the mRNA and protein levels were then assayed with reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The levels of heat shock protein 90 (HSP90), phosphorylated AKT, phosphorylated IκBα and nuclear NF-κB were assessed with immunoblot assays; the involvement of these molecules in the signaling pathway were further assessed by using specific inhibitor for HSP90, AKT or NF-κB.
  
  
  RESULTS
  Mild heat shock increased the production of inflammatory cytokines, IL-1β and IL-6. Mild heat shock increased expression of HSP90, which increased the phosphorylation of AKT. The activated AKT then increased the phosphorylation of IκBα, resulting in nuclear translocation of NF-κB, which up-regulated the expression of IL-1β and IL-6 in SIRC cells.
  
  
  CONCLUSIONS
  These findings suggest a critical role for the HSP90-AKT-NF-κB signaling pathway in mild heat shock-induced inflammatory response of cornea cells.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Ming-Ju
authors: MJ
authors: Tsai
authors: Ya-Ling
authors: YL
authors: Hsu
authors: Kwou-Yeung
authors: KY
authors: Wu
authors: Rei-Cheng
authors: RC
authors: Yang
authors: Yi-Jen
authors: YJ
authors: Chen
authors: Hsin-Su
authors: HS
authors: Yu
authors: Po-Lin
authors: PL
authors: Kuo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D018869:Heat-Shock Response / Q000276:immunology*; D051550:I-kappa B Kinase / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007634:Keratitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000276:immunology
chemical_list: D018841:HSP90 Heat-Shock Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase