title: Secretoglobin 3A2 attenuates lipopolysaccharide-induced inflammation through inhibition of ERK and JNK pathways in bronchial epithelial cells.
abstract: Secretoglobin (SCGB) 3A2, previously known as uteroglobin-related protein 1, is a secreted protein highly expressed in the epithelial cells of the airways. It has been demonstrated that SCGB3A2 is involved in allergic airway inflammation such as bronchial asthma. However, the role of SCGB3A2 in lipopolysaccharide (LPS)-induced airway inflammation has yet to be reported. The goal of this study was therefore to clarify the role of SCGB3A2 in LPS-induced airway inflammation. We stimulated BEAS-2B, human bronchial epithelial cells, with LPS and analyzed messenger RNA (mRNA) expression of tumor necrosis factor (TNF)-α and CXCL8 with or without pre-incubation of SCGB3A2. The mRNA expression of TNF-α and CXCL8 was clearly upregulated 3 h after LPS stimulation, and pre-incubation of SCGB3A2 significantly inhibited the upregulation of the mRNA expression. The pre-incubation of SCGB3A2 also inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase in BEAS-2B cells. Furthermore, PD98059, a specific inhibitor for ERK, as well as SP600125, a specific inhibitor for JNK, inhibited LPS-induced mRNA upregulation of inflammatory mediators. These results demonstrate the novel biological activity of SCGB3A2, which is that it attenuates LPS-induced inflammation in bronchial epithelial cells through inhibition of ERK and JNK activation.
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan.
authors.forename: Xintao
authors.initials: X
authors.lastname: Wang
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tanino
authors.forename: Suguru
authors.initials: S
authors.lastname: Sato
authors.forename: Takefumi
authors.initials: T
authors.lastname: Nikaido
authors.forename: Kenichi
authors.initials: K
authors.lastname: Misa
authors.forename: Naoko
authors.initials: N
authors.lastname: Fukuhara
authors.forename: Atsuro
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Junpei
authors.initials: J
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.forename: Teizo
authors.initials: T
authors.lastname: Fujita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000201:enzymology*; D060765:Secretoglobins / Q000096:biosynthesis / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; C449940:SCGB3A2 protein, human; D060765:Secretoglobins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases