TP receptor-mediated release of eosinophil chemotactic activity from human bronchial smooth muscle cells

Eur J Pharmacol. 2008 Dec 14;600(1-3):133-9. doi: 10.1016/j.ejphar.2008.09.044. Epub 2008 Oct 8.

Abstract

There are reports indicating that thromboxane A(2) receptors (TP receptors) may stimulate the eosinophil accumulation in the lower airways of asthmatics, however, the mechanisms behind such an effect remain unknown. We quantified the synthesis of eosinophil chemotactic activity and eosinophilic CC chemokines, including CCL5, CCL7, CCL8, CCL11, CCL13, CCL24, and CCL26 in primary cultures of human bronchial smooth muscle cells (BSMC) stimulated with a prostanoid TP receptor agonist, IBOP (10(-9)-10(-7) M). The activation of prostanoid TP receptors in BSMC induced the release of potent eosinophil chemoattractant(s) in the presence of interleukin (IL)-4. CCL11/eotaxin-1 was the only synthesis significantly increased by IBOP co-stimulated with IL-4, and pretreatment with an anti-CCL11 antibody abrogated the eosinophil chemotactic activity released from IBOP/IL-4-stimulated BSMC. The effect of IBOP was also completely blocked by pretreatment with a prostanoid TP receptor-specific antagonist, AA-2414. IBOP had no effect on the expression of IL-4 receptor-alpha, or on the IL-4-induced phosphorylation of STAT6 in BSMC. In conclusion, activation of prostanoid TP receptors in a Th2-dominant microenvironment might exacerbate the eosinophilic inflammation of the airways by synthesis and release of CCL11 from BSMC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / physiopathology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Bronchi / cytology
  • Bronchi / metabolism
  • Cells, Cultured
  • Chemokine CCL11 / metabolism
  • Chemokines, CC / metabolism*
  • Chemotaxis, Leukocyte / physiology
  • Eosinophils / metabolism*
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Interleukin-4 / pharmacology
  • Myocytes, Smooth Muscle / metabolism*
  • Receptors, Thromboxane A2, Prostaglandin H2 / agonists
  • Receptors, Thromboxane A2, Prostaglandin H2 / metabolism*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Chemokine CCL11
  • Chemokines, CC
  • Fatty Acids, Unsaturated
  • Receptors, Thromboxane A2, Prostaglandin H2
  • 7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid
  • Interleukin-4