Interleukin-4, interleukin-13, signal transducer and activator of transcription factor 6, and allergic asthma.
Interleukin (IL)-4 and IL-13 share many biological activities. To some extent, this is because they both signal via a shared receptor, IL-4Ralpha. Ligation of IL-4Ralpha results in activation of Signal Transducer and Activator of Transcription factor 6 (STAT6) and Insulin Receptor Substrate (IRS) molecules. In T- and B-cells, IL-4Ralpha signaling contributes to cell-mediated and humoral aspects of allergic inflammation. It has recently become clear that IL-4 and IL-13 produced in inflamed tissues activate signaling in normally resident cells of the airway. The purpose of this review is to critically evaluate the contributions of IL-4- and IL-13-induced tissue responses, especially those mediated by STAT6, to some of the pathologic features of asthma including eosinophilic inflammation, airway hyperresponsiveness, subepithelial fibrosis and excessive mucus production. We also review the functions of some recently identified IL-4- and/or IL-13-induced mediators that provide some detail on molecular mechanisms and suggest an important contribution to host defense.
Kuperman
Douglas A
DA
Northwestern University Feinberg School of Medicine, Department of Medicine, Division of Allergy-Immunology, Chicago, Illinois 60611, USA. d-kuperman@northwestern.edu
Schleimer
Robert P
RP
D000818:Animals; D001249:Asthma / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018793:Interleukin-13; D050800:STAT6 Transcription Factor; D015847:Interleukin-4