Induction of interleukin 8 by American cockroach allergens from human airway epithelial cells via extracellular signal regulatory kinase and jun N-terminal kinase but not p38 mitogen-activated protein kinase

Background Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G protein–linked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. Objective To...

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Veröffentlicht in:Annals of allergy, asthma, & immunology asthma, & immunology, 2010-09, Vol.105 (3), p.234-240
Hauptverfasser: Lee, Mey-Fann, PhD, Wang, Nancy M., PhD, Liu, Szu-Wei, MS, Lin, Shyh-Jye, MS, Chen, Yi-Hsing, MD, PhD
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Sprache:eng
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Zusammenfassung:Background Cockroaches are potent aeroallergens associated with asthma. Several reports suggest that a novel group of G protein–linked receptors, protease-activated receptors (PARs), may be involved in the intracellular signaling pathway induced by aeroallergens of the epithelial cells. Objective To investigate the mechanisms of American cockroach allergens (CraA) on interleukin 8 (IL-8) in human pulmonary epithelial cells. Methods Protease activities of CraA were quantified by the Azocoll method. The gene and protein expressions of IL-8 from CraA-stimulated A549 cells were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) was assessed by Western blot. Results CraA-induced A549 cell IL-8 secretion in a dose-dependent manner at both the messenger RNA and protein levels. CraA-induced IL-8 secretion can be blocked by serine protease inhibitors, phenylmethane sulfonyl fluoride, and aprotinin but not by other protease inhibitors. Blocking antibodies against the cleavage sites of PAR-2 and PAR-3, but not of PAR-1, inhibited CraA-induced IL-8 production. CraA induced significant PAR-2 and PAR-3 messenger RNA upregulation and extracellular-regulated kinase (ERK/1/2) and Jun N-terminal kinase (JNK) phosphorylation but not p38 MAPK. Furthermore, ERK1/2 (U0126) and JNK (SP600125) inhibitors inhibited CraA-induced IL-8 secretion by 100% and 45%, respectively. Conclusions Both PAR-2 and PAR-3 might play a role in CraA-induced IL-8 secretion from human airway epithelial cells. It signals mainly through the ERK1/2 and partly from the JNK pathways. The key receptors and signaling molecules mediate cytokine release from the respiratory epithelium and can be potential therapeutic targets in treating cockroach allergy.
ISSN:1081-1206
1534-4436
DOI:10.1016/j.anai.2010.07.008