TY - JOUR
T1 - Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro
AU - Zheng, Tao
AU - Zhu, Zhou
AU - Liu, Wei
AU - Lee, Chun Geun
AU - Chen, Qingsheng
AU - Homer, Robert J.
AU - Elias, Jack A.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Background: IL-13 signals via a high-affinity receptor that includes IL-4Rα and IL-13Rα1 and binds to the decoy receptor IL-13Rα2. The processes that regulate the expression of these receptor subunits, however, are poorly defined. Objective: These studies were designed to define the regulation of IL-13R components by TH2 and TH1 cytokines in vivo and in vitro. Methods: Northern analysis, in situ hybridization, RT-PCR analysis, and immunoprecipitation were used to define the expression of IL-13Rα1 and IL-13Rα2 in lungs from lung targeted overexpression mice and lung fragments and cells in culture. Results: IL-13Rα2 and IL-13Rα1 mRNA were detected at modest levels in lungs from control mice. In contrast, transgenic IL-13 caused a marked increase in IL-13Rα2 and IL-13Rα1 mRNA; this was most prominent in airway epithelial cells and macrophages. The effects of IL-13 on IL-13Rα2 were associated with comparable increases in protein production and were mediated by a blood leukocyte-independent and IL-4Rα-dependent mechanism. IL-13 stimulation of IL-13Rα1 was mediated via a blood leukocyte-dependent and partially IL-4Rα-dependent pathway. These effects were not specific for IL-13, because transgenic IL-4, IL-10, and IFN-γ also stimulated IL-13Rα2 mRNA accumulation while stimulating - not altering and inhibiting - IL-13Rα1 mRNA accumulation, respectively. These regulatory events were mediated, at least in part, by direct effects of these cytokines, because IL-13, IL-4, and IFN-γ had similar effects on IL-13Rα2 and/or IL-13Rα1 in epithelial cells and macrophages in in vitro culture. Conclusion: IL-13Rα2 and IL-13Rα1 are highly regulated in vivo and in vitro. These regulatory events might control IL-13 responses at sites of inflammation.
AB - Background: IL-13 signals via a high-affinity receptor that includes IL-4Rα and IL-13Rα1 and binds to the decoy receptor IL-13Rα2. The processes that regulate the expression of these receptor subunits, however, are poorly defined. Objective: These studies were designed to define the regulation of IL-13R components by TH2 and TH1 cytokines in vivo and in vitro. Methods: Northern analysis, in situ hybridization, RT-PCR analysis, and immunoprecipitation were used to define the expression of IL-13Rα1 and IL-13Rα2 in lungs from lung targeted overexpression mice and lung fragments and cells in culture. Results: IL-13Rα2 and IL-13Rα1 mRNA were detected at modest levels in lungs from control mice. In contrast, transgenic IL-13 caused a marked increase in IL-13Rα2 and IL-13Rα1 mRNA; this was most prominent in airway epithelial cells and macrophages. The effects of IL-13 on IL-13Rα2 were associated with comparable increases in protein production and were mediated by a blood leukocyte-independent and IL-4Rα-dependent mechanism. IL-13 stimulation of IL-13Rα1 was mediated via a blood leukocyte-dependent and partially IL-4Rα-dependent pathway. These effects were not specific for IL-13, because transgenic IL-4, IL-10, and IFN-γ also stimulated IL-13Rα2 mRNA accumulation while stimulating - not altering and inhibiting - IL-13Rα1 mRNA accumulation, respectively. These regulatory events were mediated, at least in part, by direct effects of these cytokines, because IL-13, IL-4, and IFN-γ had similar effects on IL-13Rα2 and/or IL-13Rα1 in epithelial cells and macrophages in in vitro culture. Conclusion: IL-13Rα2 and IL-13Rα1 are highly regulated in vivo and in vitro. These regulatory events might control IL-13 responses at sites of inflammation.
KW - Asthma
KW - IL-10
KW - IL-13 receptor
KW - IL-13 transgenic mouse
KW - IL-4
KW - Interleukin 13
KW - T2 cytokine
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U2 - 10.1067/mai.2003.1383
DO - 10.1067/mai.2003.1383
M3 - Article
C2 - 12704349
AN - SCOPUS:0037393502
SN - 0091-6749
VL - 111
SP - 720
EP - 728
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -