Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia

Yuko Matsunaga, Satoru Fukuyama, Toshiaki Okuno, Fumiyuki Sasaki, Takehiko Matsunobu, Yukari Asai, Koichiro Matsumoto, Kazuko Saeki, Masahiro Oike, Yukari Sadamura, Kentaro Machida, Yoichi Nakanishi, Masato Kubo, Takehiko Yokomizo, Hiromasa Inoue

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD 4+ T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN) in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4+ T cells in vitro. Expression of BLT2 mRNA in CD4+ T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4+ T cells may contribute to the pathophysiology of asthma.

Original languageEnglish
Pages (from-to)3306-3314
Number of pages9
JournalFASEB Journal
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 2013

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Leukotriene B<sub>4</sub> receptor BLT2 negatively regulates allergic airway eosinophilia'. Together they form a unique fingerprint.

Cite this