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 language | English |
|---|---|
| Pages (from-to) | 147-154 |
| Number of pages | 8 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 2006 |
| Externally published | Yes |
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Keywords
- Airway hyperresponsiveness
- IFN-γ
- IL-12
- RANTES (CCL5)
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Pulmonary and Respiratory Medicine
Cite this
RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge. / Koya, Toshiyuki; Takeda, Katsuyuki; Kodama, Taku; Miyahara, Nobuaki; Matsubara, Shigeki; Balhorn, Annette; Joetham, Anthony; Dakhama, Azzedine; Gelfand, Erwin W.
In: American Journal of Respiratory Cell and Molecular Biology, Vol. 35, No. 2, 08.2006, p. 147-154.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RANTES (CCL5) regulates airway responsiveness after repeated allergen challenge
AU - Koya, Toshiyuki
AU - Takeda, Katsuyuki
AU - Kodama, Taku
AU - Miyahara, Nobuaki
AU - Matsubara, Shigeki
AU - Balhorn, Annette
AU - Joetham, Anthony
AU - Dakhama, Azzedine
AU - Gelfand, Erwin W.
PY - 2006/8
Y1 - 2006/8
N2 - 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.
AB - 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.
KW - Airway hyperresponsiveness
KW - IFN-γ
KW - IL-12
KW - RANTES (CCL5)
UR - http://www.scopus.com/inward/record.url?scp=33746787729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746787729&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2005-0394OC
DO - 10.1165/rcmb.2005-0394OC
M3 - Article
C2 - 16528011
AN - SCOPUS:33746787729
VL - 35
SP - 147
EP - 154
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 2
ER -