EGF receptor activation during allergic sensitization affects IL-6-induced T-cell influx to airways in a rat model of asthma.
EGF receptor (EGFR) is involved in cell differentiation and proliferation in airways and may trigger cytokine production by T cells. We hypothesized that EGFR inhibition at the time of allergic sensitization may affect subsequent immune reactions. Brown Norway rats were sensitized with OVA, received the EGFR tyrosine kinase inhibitor, AG1478 from days 0 to 7 and OVA challenge on day 14. OVA-specific IgE in serum and cytokines and chemokines in BAL were measured 24 h after challenge. To evaluate effects on airway hyperresponsiveness (AHR), rats were sensitized, treated with AG1478, intranasally challenged, and then AHR was assessed. Furthermore chemotactic activity of BALF for CD4(+) T cells was examined. The eosinophils, neutrophils and lymphocytes in BAL were increased by OVA and only the lymphocytes were reduced by AG1478. OVA significantly enhanced IL-6 concentration in BAL, which was inhibited by AG1478. However AHR, OVA-specific IgE and IL-4 mRNA expression in CD4(+) T cells were not affected by AG1478. BALF from OVA-sensitized/challenged rats induced CD4(+) T-cell migration, which was inhibited by both AG1478 treatment in vivo and neutralization of IL-6 in vitro. EGFR activation during sensitization may affect the subsequent influx of CD4(+) T cells to airways, mainly mediated through IL-6.
Tsuchiya
Kimitake
K
Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada.
Jo
Taisuke
T
Takeda
Naoya
N
Al Heialy
Saba
S
Siddiqui
Sana
S
Shalaby
Karim Hamdy
KH
Risse
Paul-André
PA
Maghni
Karim
K
Martin
James G
JG
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011799:Quinazolines; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D020032:Tyrphostins / Q000494:pharmacology
D000485:Allergens; D016207:Cytokines; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D011799:Quinazolines; D020032:Tyrphostins; C101044:RTKI cpd; D010047:Ovalbumin; D066246:ErbB Receptors