RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge

Toshiyuki Koya, Katsuyuki Takeda, Taku Kodama, Nobuaki Miyahara, Shigeki Matsubara, Annette Balhorn, Anthony Joetham, Azzedine Dakhama, Erwin W. Gelfand

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

RANTES (CC chemokine ligand 5) contributes to airway inflammation through accumulation of eosinophils, but the exact role of RANTES (CCLS) is not defined. C57BL/6 mice, sensitized by injection of ovalbumin (OVA) on Days 1 and 14, were challenged with OVA on Days 28, 29, and 30 (3 challenges, short-term-challenge model) or on Days 28, 29, 30, 36, 40, 44, and 48 (7 challenges, repeated-challenge model) and evaluated 48 h later. Anti-mouse RANTES was given intravenously, and recombinant mouse RANTES or PBS was given intratracheally. These reagents were given on Days 28, 29, and 30 in the short-term-challenge study and on Days 44 and 48 in the repeated-challenge study. After short-term challenge, there were no effects after administration of anti-RANTES or RANTES. In the repeated-challenge study, although control mice showed a decrease in airway hyperresponsiveness, administration of anti-RANTES sustained and enhanced airway hyperresponsiveness and increased goblet cell numbers. In contrast, administration of RANTES normalized airway function but reduced goblet cell numbers. IL-12 and IFN-γ levels in BAL decreased in the anti-RANTES group and increased in the RANTES group. IFN-γ-producing CD4 T cells in lung, and IFN-γ production from lung T cells in response to OVA in the anti-RANTES group, were significantly decreased but were increased in the RANTES group. Anti-IFN-γ, administered with RANTES, decreased the effects of RANTES on AHR after repeated challenge. These data indicate that RANTES plays a role in the regulation of airway function after repeated allergen challenge, in part through modulation of levels of IFN-γ and IL-12.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume35
Issue number2
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

Keywords

  • Airway hyperresponsiveness
  • IFN-γ
  • IL-12
  • RANTES (CCL5)

ASJC Scopus subject areas

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

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