PLoS ONE (Jul 2009)

Proinflammatory and Th2 cytokines regulate the high affinity IgE receptor (FcepsilonRI) and IgE-dependant activation of human airway smooth muscle cells.

  • Naresh Singh Redhu,
  • Ali Saleh,
  • Lianyu Shan,
  • William T Gerthoffer,
  • Sam K Kung,
  • Andrew J Halayko,
  • Bouchaib Lamkhioued,
  • Abdelilah S Gounni

DOI
https://doi.org/10.1371/journal.pone.0006153
Journal volume & issue
Vol. 4, no. 7
p. e6153

Abstract

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BACKGROUND:The high affinity IgE receptor (FcepsilonRI) is a crucial structure for IgE-mediated allergic reactions. We have previously demonstrated that human airway smooth muscle (ASM) cells express the tetrameric (alphabetagamma2) FcepsilonRI, and its activation leads to marked transient increases in intracellular Ca(2+) concentration, release of Th-2 cytokines and eotaxin-1/CCL11. Therefore, it was of utmost importance to delineate the factors regulating the expression of FcepsilonRI in human (ASM) cells. METHODOLOGY/PRINCIPAL FINDINGS:Incubation of human bronchial and tracheal smooth muscle (B/TSM) cells with TNF-alpha, IL-1beta or IL-4 resulted in a significant increase in FcepsilonRI-alpha chain mRNA expression (p<0.05); and TNF-alpha, IL-4 enhanced the FcepsilonRI-alpha protein expression compared to the unstimulated control at 24, 72 hrs after stimulation. Interestingly, among all other cytokines, only TNF-alpha upregulated the FcepsilonRI-gamma mRNA expression. FcepsilonRI-gamma protein expression remained unchanged despite the nature of stimulation. Of note, as a functional consequence of FcepsilonRI upregulation, TNF-alpha pre-sensitization of B/TSM potentially augmented the CC (eotaxin-1/CCL11 and RANTES/CCL5, but not TARC/CCL17) and CXC (IL-8/CXCL8, IP-10/CXCL10) chemokines release following IgE stimulation (p<0.05, n = 3). Furthermore, IgE sensitization of B/TSM cells significantly enhanced the transcription of selective CC and CXC chemokines at promoter level compared to control, which was abolished by Lentivirus-mediated silencing of Syk expression. CONCLUSIONS/SIGNIFICANCE:Our data depict a critical role of B/TSM in allergic airway inflammation via potentially novel mechanisms involving proinflammatory, Th2 cytokines and IgE/FcepsilonRI complex.