title: Chitinase induce the release of IL-8 in human airway epithelial cells, via Ca2+-dependent PKC and ERK pathways.
abstract: Chitinases are produced in significant quantities by hosts defending against infections with chitin-containing organisms. However, little is known about the immune response of exogenous chitinase in human epithelial cells. IL-8 has been suggested to have a role in the pathogenesis of the allergenic inflammation of bronchial asthma. We examined whether Streptomyces griseus (S. griseus) chitinase-induced IL-8 on airway epithelium and identified the involvement of intracellular signalling pathways. H292 cells were treated with S. griseus chitinase with different concentrations and times. The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction. Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to S. griseus chitinase. Cells exposed to S. griseus chitinase showed higher level of IL-8 protein production and mRNA expression. Cells stimulated by S. griseus chitinase resulted in the activation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-B (NF-kB) pathways. Inhibitors of Ca(2+)-dependent PKC (Ro-31-8220, calphostin C and Go6976) significantly abolished chitinase-induced expression of IL-8. However, Ca(2+)-independent PKC inhibitor (rottlerin) did not inhibit IL-8 expression. Through ERK inhibitor (U0126) and NF-kB inhibitor (caffeine acid phenethyl ester) treatment, it was proven that ERK and NF-kB regulated chitinase-induced IL-8 expression. We concluded that S. griseus chitinase-induced IL-8 expression was regulated by the activation of Ca(2+/-)-dependent PKC, ERK and NF-kB in human airway epithelial cells.
authors.affiliation: Department of Pediatrics and Institute of Allergy, Severance Medical Research Institute, Brain Korea 21 Project for Medical science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Hong
authors.forename: K E
authors.initials: KE
authors.lastname: Lee
authors.forename: K W
authors.initials: KW
authors.lastname: Kim
authors.forename: M H
authors.initials: MH
authors.lastname: Sohn
authors.forename: K-E
authors.initials: KE
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D002688:Chitinases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000276:immunology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D009281:Naphthalenes / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000276:immunology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020545:Respiratory Mucosa / Q000201:enzymology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D002070:Butadienes; D002109:Caffeic Acids; D002227:Carbazoles; D007211:Indoles; D016209:Interleukin-8; D016328:NF-kappa B; D009281:Naphthalenes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C113580:U 0126; C081021:Go 6976; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D002688:Chitinases; C055494:caffeic acid phenethyl ester; C058819:calphostin C; D010626:Phenylethyl Alcohol; C064758:Ro 31-8220