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


RESULTS
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
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.
Redhu
Naresh Singh
NS
Department of Immunology, Section of Respiratory Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
Saleh
Ali
A
Shan
Lianyu
L
Gerthoffer
William T
WT
Kung
Sam K
SK
Halayko
Andrew J
AJ
Lamkhioued
Bouchaib
B
Gounni
Abdelilah S
AS
D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D018836:Inflammation Mediators / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D017455:Receptors, IgE; D007073:Immunoglobulin E