title: Low molecular weight hyaluronan, via AP-1 and NF-κB signalling, induces IL-8 in transformed bronchial epithelial cells.
abstract: OBJECTIVE
  New evidence demonstrated that high tidal volume mechanical ventilation results in substantial bronchial airway mechanical strain. In addition, high tidal volume mechanical ventilation has been shown to increase IL-8 production in a mechanism mediated, at least in part, by low molecular weight hyaluronan (LWM-HA). In the present study, it was investigated whether LMW-HA synthesised in the lung, in response to cyclic stretch, increased IL-8 production in the bronchial epithelium.
  
  
  METHODS
  This question was approached by stimulating a transformed human bronchial epithelial cell line with LMW-HA isolated from stretched human lung fibroblasts and probed for the activation of extracellular signal-regulated kinase pathways.
  
  
  RESULTS
  LMW-HA increased IL-8 secretion in transformed bronchial epithelial cells. Additionally, LMW-HA augmented the levels of phospho c-Jun NH2-terminal kinase (JNK) and phospho extracellular signal-regulated kinase 1/2 (ERK1/2), and also mobilised nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) from the cytoplasm to the nucleus. The inhibition of JNK, ERK1/2 and NF-κB blocked IL-8 secretion in response to LMW-HA.
  
  
  CONCLUSIONS
  The data suggest that LMW-HA produced by lung fibroblasts in response to cyclic stretch increases the secretion of IL-8 in transformed bronchial epithelial cells via AP-1 and NF-κB signalling pathways. These findings support the hypothesis that LMW-HA plays an active role in acute lung inflammation triggered by mechanical strain.
authors: Pulmonary and Critical Care Unit, Dept. of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, USA. cdo701@jaguar1.usouthal.edu
authors: Christiaan  D
authors: C
authors: Ochoa
authors: Hari  G
authors: H
authors: Garg
authors: Charles  A
authors: C
authors: Hales
authors: Deborah  A
authors: D
authors: Quinn
mesh_terms: D001980:Bronchi / Q000293:injuries*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012121:Respiration, Artificial / Q000009:adverse effects; D013990:Tidal Volume / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D006820:Hyaluronic Acid