title: Extracellular signal-regulated kinase inhibition modulates rat annulus fibrosus cell response to interleukin-1.
abstract: METHODS
  Rat annulus fibrosus (AF) cells were activated with interleukin-1 (IL-1) with or without extracellular signal-regulated kinase (ERK) inhibition. Factors associated with the anabolic/catabolic balance of the disc were determined.
  
  
  OBJECTIVE
  To clarify the role of ERK pathway in AF cells response to IL-1.
  
  
  BACKGROUND
  IL-1 plays an important role in intervertebral disc degeneration. ERK is an important inflammatory pathway that plays a crucial role in the expression of inflammatory and catabolic genes induced by IL-1 in chondrocytes. However, the role of the ERK pathway in AF cells response to IL-1 has not been fully investigated.
  
  
  METHODS
  Rat AF cells in monolayer culture were exposed to IL-1, with or without ERK inhibition; ribonucleic acid was isolated for real time polymerase chain reaction analysis of gene expression, conditioned media analyzed for nitrite, prostaglandin E-2, and IL-6, Western blot was performed to detect the changes of protein expression.
  
  
  RESULTS
  ERK specific inhibitor U0126 significantly inhibited IL-1-induced ERK activation. IL-1-dependent upregulation of iNOS, IL-6, Cox-2, (MMP)-3, and MMP-13 was significantly reduced by ERK inhibition. The decreased gene expression of collagen I, collagen II, collagen IX, and IGF-1 induced by IL-1 was also reversed by U0126. Gene expression of ADAMTS-4, ADAMTS-5, and TGF-b were not affected by IL-1 or ERK inhibition. IL-1 moderately upregulated aggrecan and TIMP-1 expression, ERK inhibition had no significant effect on aggrecan expression but decreased TIMP-1 expression in the presence of IL-1. ERK inhibition reversed the changes of protein expression of MMP-3, MMP-13, TIMP-1, aggrecan and collagen II induced by IL-1. IL-1-induced nitric oxide, prostaglandin E-2, and IL-6 accumulation were also reduced by ERK inhibition.
  
  
  CONCLUSIONS
  These results suggest that IL-1 induces an imbalance between anabolic and catabolic events in AF cells, ERK inhibition could provide some protection against the adverse effects of IL-1.
  
  
  METHODS
  N/A.
authors.affiliation: Department of orhopedic surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wei
authors.forename: Wu
authors.initials: W
authors.lastname: Zhi-Hong
authors.forename: Qiu
authors.initials: Q
authors.lastname: Gui-Xing
authors.forename: Yu
authors.initials: Y
authors.lastname: Bin
authors.forename: Chen
authors.initials: C
authors.lastname: Jun
authors.forename: Wang
authors.initials: W
authors.lastname: Yi-Peng
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002070:Butadienes / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015151:Immunoblotting; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; D002070:Butadienes; D024042:Collagen Type I; D007375:Interleukin-1; D009570:Nitriles; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; C113580:U 0126; D007334:Insulin-Like Growth Factor I; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3