title: rIL-10 enhances IL-10 signalling proteins in foetal alveolar type II cells exposed to hyperoxia.
abstract: Although the mechanisms by which hyperoxia promotes bronchopulmonary dysplasia are not fully defined, the inability to maintain optimal interleukin (IL)-10 levels in response to injury secondary to hyperoxia seems to play an important role. We previously defined that hyperoxia decreased IL-10 production and pre-treatment with recombinant IL-10 (rIL-10) protected these cells from injury. The objectives of these studies were to investigate the responses of IL-10 receptors (IL-10Rs) and IL-10 signalling proteins (IL-10SPs) in hyperoxic foetal alveolar type II cells (FATIICs) with and without rIL-10. FATIICs were isolated on embryonic day 19 and exposed to 65%-oxygen for 24 hrs. Cells in room air were used as controls. IL-10Rs protein and mRNA were analysed by ELISA and qRT-PCR, respectively. IL-10SPs were assessed by Western blot using phospho-specific antibodies. IL-10Rs protein and mRNA increased significantly in FATIICs during hyperoxia, but JAK1 and TYK2 phosphorylation showed the opposite pattern. To evaluate the impact of IL-8 (shown previously to be increased) and the role of IL-10Rs, IL-10SPs were reanalysed in IL-8-added normoxic cells and in the IL-10Rs' siRNA-treated hyperoxic cells. The IL-10Rs' siRNA-treated hyperoxic cells and IL-8-added normoxic cells showed the same pattern in IL10SPs with the hyproxic cells. And pre-treatment with rIL-10 prior to hyperoxia exposure increased phosphorylated IL-10SPs, compared to the rIL-10-untreated hyperoxic cells. These studies suggest that JAK1 and TYK2 were significantly suppressed during hyperoxia, where IL-8 may play a role, and rIL-10 may have an effect on reverting the suppressed JAK1 and TYK2 in FATIICs exposed to hyperoxia.
authors.affiliation: Department of Pediatrics, Dongtan Jeil Women and Infants' Hospital, Whasung, South Korea.|Institute of Medical Sciences, Kangwon National University School of Medicine, Chuncheon, Kangwon, South Korea.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Medical and Bio-Materials Research Center, Kangwon National University School of Medicine, Chuncheon, Kangwon, South Korea.
authors.forename: Dong Gun
authors.initials: DG
authors.lastname: Lee
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005333:Fetus / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018496:Hyperoxia / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D053701:Receptors, Interleukin-10; D011994:Recombinant Proteins; D016753:Interleukin-10; D010100:Oxygen
keywords: IL-10 receptors; IL-10 signalling proteins; IL-8; foetal alveolar type II cells; hyperoxia