Retinoic acid attenuates lipopolysaccharide-induced inflammatory responses by suppressing TLR4/NF-[kappa]B expression in rat mammary tissue

• Published in: International immunopharmacology Vol. 10; no. 7; pp. 799 - 805
• Main Authors: Gu, Beibei, Miao, Jinfeng, Fa, Yanmei, Lu, Jingye, Zou, Sixiang
• Format: Journal Article
• Language: English
• Published: 01.07.2010
• ISSN: 1567-5769
• DOI: 10.1016/j.intimp.2010.04.022

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-[kappa]B 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-[kappa]B DNA binding activity and the level of IL-1b in the mammary gland. The animal study result was confirmed by an in vitro cell culture system trial. TLR4 protein expression and NF-[kappa]B DNA binding activity were significantly decreased in primary rat mammary epithelial cells pretreated with 1 kmol/l retinoic acid at 1 h post-LPS stimulation. IL-1b gene expression was also significantly decreased at 2, 4 and 8 h 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-[kappa]B 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.