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- 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.
- Authors
Shao, Zhen-Jun; Zheng, Xiao-Wei; Feng, Ting; Huang, Juan; Chen, Jian; Wu, Yi-Ying; Zhou, Li-Ming; Tu, Wen-Wei; Li, Hong
- 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.
- Subjects
ANTI-infective agents; DEFENSINS; MITOGEN-activated protein kinases; LABDANES; DITERPENES; EPITHELIAL cells; MESSENGER RNA; GENE expression
- Publication
Canadian Journal of Physiology & Pharmacology, 2012, Vol 90, Issue 5, p647
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/y2012-050