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

Respir Res. 2008 Apr 1;9(1):30. doi: 10.1186/1465-9921-9-30.

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives
  • Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
  • Bronchi / drug effects
  • Bronchi / immunology
  • Bronchi / metabolism
  • Bronchi / microbiology*
  • Cells, Cultured
  • Chemokine CCL11 / metabolism*
  • Diglycerides / pharmacology
  • Escherichia coli / pathogenicity*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Interleukin-8 / metabolism*
  • Lipopeptides
  • Lipopolysaccharides / pharmacology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / immunology
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / microbiology*
  • Nod1 Signaling Adaptor Protein / metabolism
  • Nod2 Signaling Adaptor Protein / metabolism
  • Oligopeptides / pharmacology
  • Peptides / pharmacology
  • Poly I-C / pharmacology
  • Staphylococcus aureus / pathogenicity*
  • Tacrolimus / pharmacology
  • Time Factors
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • CCL11 protein, human
  • CXCL8 protein, human
  • Chemokine CCL11
  • Diglycerides
  • FSL-1 lipoprotein, synthetic
  • Interleukin-1beta
  • Interleukin-8
  • Lipopeptides
  • Lipopolysaccharides
  • NOD1 protein, human
  • NOD2 protein, human
  • Nod1 Signaling Adaptor Protein
  • Nod2 Signaling Adaptor Protein
  • Oligopeptides
  • Pam(3)CSK(4) peptide
  • Peptides
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Acetylmuramyl-Alanyl-Isoglutamine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Poly I-C
  • Tacrolimus