title: Interleukin 6 augments mechanical strain-induced C-reactive protein synthesis via the stretch-activated channel-nuclear factor κ B signal pathway.
abstract: OBJECTIVE
  C-reactive protein (CRP), an inflammation marker, is a strong independent risk factor for cardiovascular disease. Vessels are able to express CRP; however, the molecular mechanism behind this expression is not clear.
  
  
  METHODS
  Reverse transcription PCR and ELISA were used to detect messenger RNA and proteins of CRP and nuclear factor κB (NF-κB) activity in vessel rings stretched with different mechanical strains.
  
  
  RESULTS
  Interleukin (IL)-6 treatment did not induce CRP expression in vessel rings of white rabbits in the absence of mechanical strain. In contrast, IL-6 augmented CRP expression in vessel rings stretched with mechanical strains of 3 and 5 g (CRP mRNA, IL-6: 11.367±1.68 and 12.78±0.76 vs vehicle: 7.27±0.88 and 8.3±0.91 folds, respectively; CRP, IL-6: 12.79±1.62 and 14.05±2.1 vs vehicle: 7.72±1.04 and 8.16±1.52 folds, respectively; p<0.05 vs 0 g group and vehicle control group; n=5), and this effect was completely blocked by treatment with gadolinium III chloride hexahydrate (GdCl3). Moreover, IL-6 treatment increased NF-κB activity in vessels stretched with a mechanical strain of 3 g, and this effect was blocked by stretch-activated channel inhibitors (streptomycin or GdCl3) and the NF-κB peptide inhibitor SN50, but not by the inactive SN50 analogue SN50M. We also performed similar experiments on human internal mammary arteries and obtained similar results.
  
  
  CONCLUSIONS
  These results indicate that the inflammatory cytokine IL-6 alone does not induce CRP synthesis in vessels in the absence of mechanical strain; however, IL-6 augments mechanical strain-induced CRP synthesis in vessels via the stretch-activated channel-NF-κB pathway.
authors.affiliation: Department of Cardiology, Union Hospital, Fujian Medical University, Fujian Institute of Coronary Artery Disease, Fuzhou, Fujian, China.
authors.forename: Huaineng
authors.initials: H
authors.lastname: Zhou
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Li
authors.forename: Genya
authors.initials: G
authors.lastname: Huang
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Gu
authors.forename: Jianping
authors.initials: J
authors.lastname: Zeng
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Chufan
authors.initials: C
authors.lastname: Luo
authors.forename: Baiqin
authors.initials: B
authors.lastname: Ou
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhongkai
authors.initials: Z
authors.lastname: Wu
authors.forename: Lilong
authors.initials: L
authors.lastname: Tang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002097:C-Reactive Protein / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013307:Streptomycin / Q000494:pharmacology; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D007473:Ion Channels; D016328:NF-kappa B; D010455:Peptides; D012333:RNA, Messenger; C118258:SN50 peptide; D002097:C-Reactive Protein; D005682:Gadolinium; C038958:gadolinium chloride; D013307:Streptomycin