IL-9 induces CCL11 expression via STAT3 signalling in human airway smooth muscle cells.
BACKGROUND
Previous 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.


RESULTS
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 STAT3beta 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.


CONCLUSIONS
Taken together, our results indicate that IL-9 mediated CCL11 via STAT3 signalling pathway may play a crucial role in airway inflammatory responses.
Yamasaki
Akira
A
Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
Saleh
Ali
A
Koussih
Latifa
L
Muro
Shigeo
S
Halayko
Andrew J
AJ
Gounni
Abdelilah S
AS
D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D054413:Chemokine CCL11 / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D006801:Humans; D015151:Immunoblotting; D016906:Interleukin-9 / Q000494:pharmacology*; D008168:Lung / Q000166:cytology; D018613:Microscopy, Confocal; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D054413:Chemokine CCL11; D016906:Interleukin-9; D050796:STAT3 Transcription Factor