IgE induces proliferation in human airway smooth muscle cells: role of MAPK and STAT3 pathways

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dc.contributor.authorRedhu, Naresh S
dc.contributor.authorShan, Lianyu
dc.contributor.authorAl-Subait, Duaa
dc.contributor.authorAshdown, Heather L
dc.contributor.authorMovassagh, Hesam
dc.contributor.authorLamkhioued, Bouchaib
dc.contributor.authorGounni, Abdelilah S
dc.date.accessioned2013-11-13T10:49:24Z
dc.date.available2013-11-13T10:49:24Z
dc.date.issued2013-10-17
dc.date.updated2013-11-13T10:49:25Z
dc.description.abstractAbstract Airway remodeling is not specifically targeted by current asthma medications, partly owing to the lack of understanding of remodeling mechanisms, altogether posing great challenges in asthma treatment. Increased airway smooth muscle (ASM) mass due to hyperplasia/hypertrophy contributes significantly to overall airway remodeling and correlates with decline in lung function. Recent evidence suggests that IgE sensitization can enhance the survival and mediator release in inflammatory cells. Human ASM (HASM) cells express both low affinity (FcεRII/CD23) and high affinity IgE Fc receptors (FcεRI), and IgE can modulate the contractile and synthetic function of HASM cells. IgE was recently shown to induce HASM cell proliferation but the detailed mechanisms remain unknown. We report here that IgE sensitization induces HASM cell proliferation, as measured by 3H-thymidine, EdU incorporation, and manual cell counting. As an upstream signature component of FcεRI signaling, inhibition of spleen tyrosine kinase (Syk) abrogated the IgE-induced HASM proliferation. Further analysis of IgE-induced signaling depicted an IgE-mediated activation of Erk 1/2, p38, JNK MAPK, and Akt kinases. Lastly, lentiviral-shRNA-mediated STAT3 silencing completely abolished the IgE-mediated HASM cell proliferation. Collectively, our data provide mechanisms of a novel function of IgE which may contribute, at least in part, to airway remodeling observed in allergic asthma by directly inducing HASM cell proliferation.
dc.description.versionPeer Reviewed
dc.identifier.citationAllergy, Asthma & Clinical Immunology. 2013 Oct 17;9(1):41
dc.identifier.doihttp://dx.doi.org/10.1186/1710-1492-9-41
dc.identifier.urihttp://hdl.handle.net/1993/22255
dc.language.rfc3066en
dc.rightsopen accessen_US
dc.rights.holderNaresh Singh Redhu et al.; licensee BioMed Central Ltd.
dc.titleIgE induces proliferation in human airway smooth muscle cells: role of MAPK and STAT3 pathways
dc.typeJournal Article
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