RT Journal Article
SR Electronic
T1 Berberine decreased iNOS mRNA stability through negative regulation of HuR in LPS-induced macrophages
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.115.231043
DO 10.1124/jpet.115.231043
A1 Ji-Sun Shin
A1 Hye-Eun Choi
A1 SeungHwan Seo
A1 Jung-Hye Choi
A1 Nam-In Baek
A1 Kyung-Tae Lee
YR 2016
UL http://jpet.aspetjournals.org/content/early/2016/05/12/jpet.115.231043.abstract
AB Berberine, a major isoquinoline alkaloid found in medicinal herbs, has been reported to possess anti-inflammatory effects. However, the underlying mechanisms responsible for its actions are poorly understood. In the present study, the authors investigated the inhibitory effects of berberine and the molecular mechanisms involved in LPS-treated RAW 264.7 and THP-1 macrophages and its effects in LPS-induced septic shock in mice. In both macrophage cell types, berberine inhibited the LPS-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein expression, but had no effect on iNOS mRNA transcription. Suppression of LPS-induced iNOS protein expression by berberine occurred via a human antigen R (HuR)-mediated reduction of iNOS mRNA stability. Molecular data revealed that the suppression on the LPS-induced HuR binding to iNOS mRNA by berberine was accompanied by a reduction in nucleocytoplasmic HuR shuttling. Pretreatment with berberine reduced LPS-induced iNOS protein expression, the cytoplasmic translocation of HuR in liver tissues and increased the survival rate of mice with LPS-induced endotoxemia. These results show that the suppression of iNOS protein expression by berberine under LPS-induced inflammatory conditions is associated with a reduction in iNOS mRNA stability due to inhibition of the cytoplasmic translocation of HuR.