IgE regulates the expression of smMLCK in human airway smooth muscle cells.
Previous studies have shown that enhanced accumulation of contractile proteins such as smooth muscle myosin light chain kinase (smMLCK) plays a major role in human airway smooth muscle cells (HASM) cell hypercontractility and hypertrophy. Furthermore, serum IgE levels play an important role in smooth muscle hyperreactivity. However, the effect of IgE on smMLCK expression has not been investigated. In this study, we demonstrate that IgE increases the expression of smMLCK at mRNA and protein levels. This effect was inhibited significantly with neutralizing abs directed against FcεRI but not with anti-FcεRII/CD23. Furthermore, Syk knock down and pharmacological inhibition of mitogen activated protein kinases (MAPK) (ERK1/2, p38, and JNK) and phosphatidylinositol 3-kinase (PI3K) significantly diminished the IgE-mediated upregulation of smMLCK expression in HASM cells. Taken together, our data suggest a role of IgE in regulating smMLCK in HASM cells. Therefore, targeting the FcεRI activation on HASM cells may offer a novel approach in controlling the bronchomotor tone in allergic asthma.
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Jyoti
J
Balhara
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Naresh Singh
NS
Redhu
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Lianyu
L
Shan
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba.
Abdelilah S
AS
Gounni
D001249:Asthma / Q000201:enzymology; D002453:Cell Cycle; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006967:Hypersensitivity / Q000201:enzymology; D007073:Immunoglobulin E / Q000737:chemistry / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism
C489017:FCGR1A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D007073:Immunoglobulin E; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D009219:Myosin-Light-Chain Kinase