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Retinoic acid attenuates lipopolysaccharide-induced inflammatory responses by suppressing TLR4/NF-kappaB expression in rat mammary tissue.
MedLine Citation:
PMID:  20438866     Owner:  NLM     Status:  In-Process    
The retinoids, a group of natural or synthetic derivatives of vitamin A, exert various anti-neoplastic and immunomodulatory actions. Recent studies have demonstrated that retinoic acid protects rats against lipopolysaccharide (LPS)-induced mastitis, but the mechanism of action is unclear. In the present study, an LPS-induced rat mastitis model and primary cultures of rat mammary epithelial cells were used to investigate the effect of retinoic acid on the TLR4/NF-kappaB signaling pathway. The data indicated that toll-like receptor 4 (TLR4) gene expression reached its peak value earlier in retinoic acid-treated rats than in the control group, and that retinoic acid significantly decreased NF-kappaB DNA binding activity and the level of IL-1beta in the mammary gland. The animal study result was confirmed by an in vitro cell culture system trial. TLR4 protein expression and NF-kappaB DNA binding activity were significantly decreased in primary rat mammary epithelial cells pretreated with 1mumol/l retinoic acid at 1h post-LPS stimulation. IL-1beta gene expression was also significantly decreased at 2, 4 and 8h post-LPS stimulation. These findings demonstrate that direct action by retinoic acid leads to attenuation of the LPS-induced inflammatory response by suppression of the TLR4/NF-kappaB signalling system, thereby providing a novel explanation for the underlying effect proposed for retinoic acid in the protection of mammary tissue during LPS-induced acute mastitis.
Beibei Gu; Jinfeng Miao; Yanmei Fa; Jingye Lu; Sixiang Zou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-10
Journal Detail:
Title:  International immunopharmacology     Volume:  10     ISSN:  1878-1705     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-08-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  799-805     Citation Subset:  IM    
Copyright Information:
2010 Elsevier B.V. All rights reserved.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
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