Blocking the leukotriene B4 receptor 1 inhibits late-phase airway responses in established disease

Koichi Waseda, Nobuaki Miyahara, Arihiko Kanehiro, Genyo Ikeda, Hikari Koga, Yasuko Fuchimoto, Etsuko Kurimoto, Yasushi Tanimoto, Mikio Kataoka, Mitsune Tanimoto, Erwin W. Gelfand

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early- and late-phase development of AHR and airway inflammation in previously sensitized and challenged mice. Female BALB/c mice were sensitized (Days 1 and 14) and challenged (primary, Days 28-30) with ovalbumin. On Day 72, mice were challenged (secondary) with a single OVA aerosol, and the early and late phases of AHR and inflammation were determined. Specific blockade of BLT1 was attained by oral administration of a BLT1 antagonist on Days 70 through 72. Administration of the antagonist inhibited the secondary ovalbumin challenge-induced alterations in airway responses during the late phase but not during the early phase, as demonstrated by decreases in AHR and in bronchoalveolar lavage neutrophilia and eosinophilia 6 and 48 hours after secondary challenge. The latter was associated with decreased levels of KC protein, macrophage inflammatory protein 2, and IL-17 in the airways. These data identify the importance of the LTB4-BLT1 pathway in the development of late-phase, allergen-induced airway responsiveness after secondary airway challenge in mice with established airway disease.

Original languageEnglish
Pages (from-to)851-857
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume45
Issue number4
DOIs
Publication statusPublished - Oct 1 2011

Fingerprint

Leukotriene B4 Receptors
Leukotriene B4
Ovalbumin
Inflammation
Allergens
Chemokine CXCL2
Interleukin-17
Eosinophilia
Bronchoalveolar Lavage
Aerosols
Oral Administration
Proteins

Keywords

  • BLT1 antagonist
  • EAR
  • Established asthma
  • LAR

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Blocking the leukotriene B4 receptor 1 inhibits late-phase airway responses in established disease. / Waseda, Koichi; Miyahara, Nobuaki; Kanehiro, Arihiko; Ikeda, Genyo; Koga, Hikari; Fuchimoto, Yasuko; Kurimoto, Etsuko; Tanimoto, Yasushi; Kataoka, Mikio; Tanimoto, Mitsune; Gelfand, Erwin W.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 45, No. 4, 01.10.2011, p. 851-857.

Research output: Contribution to journalArticle

Waseda, K, Miyahara, N, Kanehiro, A, Ikeda, G, Koga, H, Fuchimoto, Y, Kurimoto, E, Tanimoto, Y, Kataoka, M, Tanimoto, M & Gelfand, EW 2011, 'Blocking the leukotriene B4 receptor 1 inhibits late-phase airway responses in established disease', American Journal of Respiratory Cell and Molecular Biology, vol. 45, no. 4, pp. 851-857. https://doi.org/10.1165/rcmb.2010-0455OC
Waseda, Koichi ; Miyahara, Nobuaki ; Kanehiro, Arihiko ; Ikeda, Genyo ; Koga, Hikari ; Fuchimoto, Yasuko ; Kurimoto, Etsuko ; Tanimoto, Yasushi ; Kataoka, Mikio ; Tanimoto, Mitsune ; Gelfand, Erwin W. / Blocking the leukotriene B4 receptor 1 inhibits late-phase airway responses in established disease. In: American Journal of Respiratory Cell and Molecular Biology. 2011 ; Vol. 45, No. 4. pp. 851-857.
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