Cytokine regulation of IL-13Ralpha2 and IL-13Ralpha1 in vivo and in vitro.
BACKGROUND
IL-13 signals via a high-affinity receptor that includes IL-4Ralpha and IL-13Ralpha1 and binds to the decoy receptor IL-13Ralpha2. 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 T(H)2 and T(H)1 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-13Ralpha1 and IL-13Ralpha2 in lungs from lung targeted overexpression mice and lung fragments and cells in culture.


RESULTS
IL-13Ralpha2 and IL-13Ralpha1 mRNA were detected at modest levels in lungs from control mice. In contrast, transgenic IL-13 caused a marked increase in IL-13Ralpha2 and IL-13Ralpha1 mRNA; this was most prominent in airway epithelial cells and macrophages. The effects of IL-13 on IL-13Ralpha2 were associated with comparable increases in protein production and were mediated by a blood leukocyte-independent and IL-4Ralpha-dependent mechanism. IL-13 stimulation of IL-13Ralpha1 was mediated via a blood leukocyte-dependent and partially IL-4Ralpha-dependent pathway. These effects were not specific for IL-13, because transgenic IL-4, IL-10, and IFN-gamma also stimulated IL-13Ralpha2 mRNA accumulation while stimulating-not altering and inhibiting-IL-13Ralpha1 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-gamma had similar effects on IL-13Ralpha2 and/or IL-13Ralpha1 in epithelial cells and macrophages in in vitro culture.


CONCLUSIONS
IL-13Ralpha2 and IL-13Ralpha1 are highly regulated in vivo and in vitro. These regulatory events might control IL-13 responses at sites of inflammation.
Zheng
Tao
T
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, USA.
Zhu
Zhou
Z
Liu
Wei
W
Lee
Chun Geun
CG
Chen
Qingsheng
Q
Homer
Robert J
RJ
Elias
Jack A
JA
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics*; D053660:Receptors, Interleukin-13
D016207:Cytokines; C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D015847:Interleukin-4; D007371:Interferon-gamma