title: Andrographolide exerted its antimicrobial effects by upregulation of human β-defensin-2 induced through p38 MAPK and NF-κB pathway in human lung epithelial cells.
abstract: Andrographis paniculata (Burm. f) Nees is a traditional herbal medicine for the treatment of infection and inflammation in China. Andrographolide (andro) is one of the major components. Human β-defensin-2 (hBD-2) is an inducible antimicrobial peptide that plays an important role in innate immunity. The present study aimed to investigate the effect of andro on upregulation of hBD-2 and the key signaling pathways involved in andro-induced hBD-2 expression. Real-time reverse transcription - PCR and Western blot assays showed that andro (1.0-10 µmol/L) can upregulate the expression of hBD-2 in a dose-dependent manner. Further studies suggested that hBD-2 mRNA and protein expression in responsive to andro were attenuated by pretreatment with SB203580 (an inhibitor of p38 mitogen-activated protein kinase (p38 MAPK)), MG-132 (an inhibitor of nuclear factor κB (NF-κB)), and an NF-κB activator inhibitor, but not by an inhibitor of ERK (PD98059) or by an inhibitor of JNK(SP600125). Moreover, we found that a second p38 MAPK inhibitor (SB202190) significantly blocked andro-mediated hBD-2 induction in SPC-A-1 lung epithelial cells. Finally, the p-c-Jun transcription factor activity assay also showed that AP-1 activity was induced by andro compared with the untreated group. We conclude that andro may exert its antimicrobial effects by upregulating the expression of hBD-2 through the p38 MAPK and NF-κB pathway.
authors.affiliation: Laboratory of Joint Research Center of WCSUH and UHK, West China Second University Hospital, Sichuan University, Chengdu, PR China.
authors.forename: Zhen-Jun
authors.initials: ZJ
authors.lastname: Shao
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Zheng
authors.forename: Ting
authors.initials: T
authors.lastname: Feng
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhou
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Tu
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; C106641:DEFB4A protein, human; D004224:Diterpenes; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D023083:beta-Defensins; C030419:andrographolide; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases