STAT-1 is activated by IL-4 and IL-13 in multiple cell types.
While interleukin-4 (IL-4) and interleukin-13 (IL-13) can utilize a common receptor, composed of IL-4Ralpha and IL-13Ralpha1, IL-4 can also signal through a receptor with IL-4Ralpha and the common gamma chain (gammaC) as its subunits. IL-4 and IL-13 have been reported to elicit similar biological effects in a number of settings, including stimulating Ig isotype switching to IgE and inducing chemokines and cytokines in a variety of cell types whereas, depending on the receptor expression on responder cells, differential effects such as induction of type II helper T cell differentiation by IL-4 but not by IL-13 are also well documented. Recent data suggest distinct roles for these two cytokines in the 'in vivo' pathology of airway inflammatory diseases such as asthma. In this study, we examined the possibility of differential signaling by IL-4 and IL-13 on cells of the airway, by comparing expression of receptor chains and activation of different Signal Transducer and Activator of Transcription (STAT) family members. Five primary cultured cell lines representing four non-immune human lung tissue cell types (smooth muscle, epithelium, endothelium, and fibroblast) were utilized. While we readily detected expression of IL-4 Ralpha and IL-13Ralpha1 in all five cell lines, gammaC was not detectable in any of these cell lines. Consistent with previous reports, we detected STAT-6 activation in all five airway tissue cell lines examined in response to both cytokines. In addition, we also consistently detected STAT-1 activation in all of these cells. This observation was extended to include lymphoid as well as myeloid cells that express also gammaC chain. In conclusion, while the study found no differences in STAT activation in response to the two cytokines, the data show that in addition to STAT-6 activation, STAT-1 activation is also a part of the integral signaling pathways utilized by IL-4 and IL-13.
Wang
I-Ming
IM
Wyeth Research, Inflammation Biology, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
Lin
Huamao
H
Goldman
Samuel J
SJ
Kobayashi
Michiko
M
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000378:metabolism*; D009928:Organ Specificity; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4