title: Differential regulation of CCL-11/eotaxin-1 and CXCL-8/IL-8 by gram-positive and gram-negative bacteria in human airway smooth muscle cells.
abstract: BACKGROUND
  Bacterial infections are a cause of exacerbation of airway disease. Airway smooth muscle cells (ASMC) are a source of inflammatory cytokines/chemokines that may propagate local airway inflammatory responses. We hypothesize that bacteria and bacterial products could induce cytokine/chemokine release from ASMC.
  
  
  METHODS
  Human ASMC were grown in culture and treated with whole bacteria or pathogen associated molecular patterns (PAMPs) for 24 or 48 h. The release of eotaxin-1, CXCL-8 or GMCSF was measured by ELISA.
  
  
  RESULTS
  Gram-negative E. coli or gram-positive S. aureus increased the release of CXCL-8, as did IL-1beta, LPS, FSL-1 and Pam3CSK4, whereas FK565, MODLys18 or Poly I:C did not. E. coli inhibited eotaxin-1 release under control conditions and after stimulation with IL-1beta. S. aureus tended to inhibit eotaxin-1 release stimulated with IL-1beta. E. coli or LPS, but not S. aureus, induced the release of GMCSF.
  
  
  CONCLUSIONS
  Gram-positive or gram-negative bacteria activate human ASMC to release CXCL-8. By contrast gram-negative bacteria inhibited the release of eotaxin-1 from human ASMCs. E. coli, but not S. aureus induced GMCSF release from cells. Our findings that ASMC can respond directly to gram-negative and gram-positive bacteria by releasing the neutrophil selective chemokine, CXCL-8, is consistent with what we know about the role of neutrophil recruitment in bacterial infections in the lung. Our findings that bacteria inhibit the release of the eosinophil selective chemokine, eotaxin-1 may help to explain the mechanisms by which bacterial immunotherapy reduces allergic inflammation in the lung.
authors.affiliation: Experimental Studies, Airway Disease Section, National Heart & Lung Institute, Imperial College London, London, SW3 6LY, UK. razao_issa@hotmail.com
authors.forename: Razao
authors.initials: R
authors.lastname: Issa
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Maria B
authors.initials: MB
authors.lastname: Sukkar
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Jane A
authors.initials: JA
authors.lastname: Mitchell
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D004926:Escherichia coli / Q000472:pathogenicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C515456:CCL11 protein, human; C508606:CXCL8 protein, human; D054413:Chemokine CCL11; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D053583:Interleukin-1beta; D016209:Interleukin-8; D055666:Lipopeptides; D008070:Lipopolysaccharides; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; C508075:Pam(3)CSK(4) peptide; D010455:Peptides; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011070:Poly I-C; D016559:Tacrolimus