title: Role of SIRT1 in Streptococcus pneumoniae-induced human β-defensin-2 and interleukin-8 expression in A549 cell.
abstract: Streptococcus pneumoniae is an important pathogen of pneumonia in human. Human alveolar epithelium acts as an effective barrier and is an active participant in host defense against invasion of bacterial by production of various mediators. Sirtuin 1 (SIRT1), the prototypic class III histone deacetylase, is involved in the molecular control of lifespans and immune responses. This study aimed at examining the role of SIRT1 in mediating S. pneumoniae-induced human β-defensin-2 (hBD2) and interleukin-8(IL-8) expression in the alveolar epithelial cell line A549 and the underlying mechanisms involved. A549 cells were infected with S. pneumoniae for indicated times. Exposure of A549 cells to S. pneumoniae increased the expressions of SIRT1 protein, hBD2 and IL-8 mRNA, and protein. The SIRT1 activator resveratrol enhanced S. pneumoniae-induced gene expression of hBD2 but decreased IL-8 mRNA levels. Blockade of SIRT1 activity by the SIRT1 inhibitors nicotinamide reduced S. pneumoniae-induced hBD2 mRNA expression but increased its stimulatory effects on IL-8 mRNA. S. pneumoniae-induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SIRT1 expression was attenuated by selective inhibitors of ERK and p38 MAPK. The hBD2 mRNA production was decreased by pretreatment with p38 MAPK inhibitor but not with ERK inhibitor, whereas the IL-8 mRNA expression was controlled by phosphorylation of ERK. These results suggest that SIRT1 mediates the induction of hBD2 and IL-8 gene expression levels in A549 cell by S. pneumoniae. SIRT1 may play a key role in host immune and defense response in A549.
authors.affiliation: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, 109 West Xueyuan Road, Lucheng District, Wenzhou, 325027, Zhejiang, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Shun-hang
authors.initials: SH
authors.lastname: Wen
authors.forename: Shu-zhen
authors.initials: SZ
authors.lastname: Guo
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Su
authors.forename: Hu-jun
authors.initials: HJ
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Chong
authors.forename: Hai-lin
authors.initials: HL
authors.lastname: Zhang
authors.forename: Wei-xi
authors.initials: WX
authors.lastname: Zhang
authors.forename: Chang-chong
authors.initials: CC
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D013997:Time Factors; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C508606:CXCL8 protein, human; C106641:DEFB4A protein, human; D020536:Enzyme Activators; D056572:Histone Deacetylase Inhibitors; D016209:Interleukin-8; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D023083:beta-Defensins; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1