IL-9 Induces CCL11 Expression via STAT3 Signalling in Human Airway Smooth Muscle Cells |
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Authors: | Akira Yamasaki Ali Saleh Latifa Koussih Shigeo Muro Andrew J. Halayko Abdelilah S. Gounni |
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Affiliation: | 1. Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.; 2. Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada.; 3. Respiratory Section, University of Manitoba, Winnipeg, Manitoba, Canada.; 4. Department of Respiratory Medicine, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan.;University of Alabama-Birmingham, United States of America |
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Abstract: | BackgroundPrevious findings support the concept that IL-9 may play a significant role in mediating both pro-inflammatory and changes in airway responsiveness that characterizes the atopic asthmatic state. We previously demonstrated that human airway smooth muscle (ASM) cells express a functional IL-9R that mediate CCL11 expression. However, the signaling pathway governing this effect is not well understood.Methodology/Principal Findings In this study, we showed that IL-9 mediated CCL11 expression in ASM cells does not rely on STAT6 or STAT5 but on STAT3 pathway. IL-9 induced rapid STAT3 activation in primary ASM cells that was not observed in case of STAT6 or STAT5. STAT3 binding to CCL11 promoter was also observed in vivo upon IL-9 stimulation of ASM cells. Disruption of STAT3 activity with SH2 domain binding inhibitory peptide results in significant reduction of IL-9 mediated CCL11 promoter activity. DN STAT3β over-expression in ASM cells, but not Ser 727 STAT3 or STAT6 DN, abolishes IL-9 mediated CCL11 promoter activity. Finally, STAT3 but not STAT6 silenced ASM cells showed significant reduction in IL-9 mediated CCL11 promoter activity and mRNA expression.Conclusion/SignificanceTaken together, our results indicate that IL-9 mediated CCL11 via STAT3 signalling pathway may play a crucial role in airway inflammatory responses. |
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