Open AccessCecropin B Represses CYP3A29 Expression through Activation of the TLR2/4-NF-κB/PXR Signaling Pathway
Author(s) -
Xiaoqiao Zhou,
Xiaowen Li,
Xiliang Wang,
Xiaodong Jin,
Deshi Shi,
Jun Wang,
Dingren Bi
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27876
Subject(s) - pregnane x receptor , cecropin , transactivation , tlr2 , nf κb , signal transduction , iκb kinase , downregulation and upregulation , receptor , microbiology and biotechnology , biology , retinoid x receptor , transcription factor , chemistry , nuclear receptor , biochemistry , gene , peptide , tlr4 , antimicrobial peptides
Cecropins are peptide antibiotics used as drugs and feed additives. Cecropin B can inhibit the expression of CYP3A29, but the underlying mechanisms remain unclear. The present study was designed to determine the mechanisms responsible for the effects of cecropin B on CYP3A29 expression, focusing on the Toll-like receptors (TLRs) and NF-κB pathways. Our results indicated that the CYP3A29 expression was inhibited by cecropin B, which was regulated by pregnane X receptor (PXR) in a time- and dose-dependent manner. Cecropin B-induced NF-κB activation played a pivotal role in the suppression of CYP3A29 through disrupting the association of the PXR/retinoid X receptor alpha (RXR-α) complex with DNA sequences. NF-κB p65 directly interacted with the DNA-binding domain of PXR, suppressed its expression, and inhibited its transactivation, leading to the downregulation of the PXR-regulated CYP3A29 expression. Furthermore, cecropin B activated pig liver cells by interacting with TLRs 2 and 4, which modulated NF-κB-mediated signaling pathways. In conclusion, cecropin B inhibited the expression of CYP3A29 in a TLR/NF-κB/PXR-dependent manner, which should be considered in future development of cecropins and other antimicrobial peptides.