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

Yusuke Suzuki, Koichiro Asano, Kyoko Niimi, Jun Miyata, Yoshiki Shiraishi, Koichi Fukunaga, Tetsuya Shiomi, Takeshi Nakajima, Tsuyoshi Oguma, Koichi Sayama, Akitoshi Ishizaka

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4 Citations (Scopus)

Abstract

There are reports indicating that thromboxane A2 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-α, 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.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalEuropean journal of pharmacology
Volume600
Issue number1-3
DOIs
Publication statusPublished - 2008 Dec 14

Keywords

  • Asthma
  • CCL11
  • CCR3
  • Chemotaxis
  • Interleukin-4

ASJC Scopus subject areas

  • Pharmacology

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    Suzuki, Y., Asano, K., Niimi, K., Miyata, J., Shiraishi, Y., Fukunaga, K., Shiomi, T., Nakajima, T., Oguma, T., Sayama, K., & Ishizaka, A. (2008). TP receptor-mediated release of eosinophil chemotactic activity from human bronchial smooth muscle cells. European journal of pharmacology, 600(1-3), 133-139. https://doi.org/10.1016/j.ejphar.2008.09.044