Gossypol but not cottonseed extracts or lipopolysaccharides stimulates HuR gene expression in mouse cells

Authors: Cao, Heping; Sethumadhavan, Kandan

Submitted to: Journal of Functional Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2019
Publication Date: 8/1/2019
Citation: Cao, H., Sethumadhavan, K. 2019. Gossypol but not cottonseed extracts or lipopolysaccharides stimulates HuR gene expression in mouse cells. Journal of Functional Foods. 59:25-29. https://doi.org/10.1016/j.jff.2019.05.022.
DOI: https://doi.org/10.1016/j.jff.2019.05.022

Interpretive Summary: The overall objective of our project was to increase the value of cottonseed products for improving human and animal nutrition and alleviating inflammatory diseases. Plant polyphenols are bioactive compounds and have been used for the prevention and treatment of various diseases since ancient history. However, there is a limited supply of plant polyphenols from natural resources. We recently isolated cottonseed extracts essentially free of toxic gossypol and showed that they can regulate diacylglycerol acyltransferase gene expression in mouse macrophages. In this study, we examined the effects of cottonseed extracts, gossypol from cottonseed and LPS from bacteria on HuR gene expression in mouse macrophages because of the importance of HuR protein in tumorigenesis and inflammation. The novel finding of the current study is that gossypol significantly increased HuR gene expression but cottonseed extracts essentially free of gossypol and LPS had only minor effect on its expression in mouse macrophages. The results strongly indicate that gossypol derived from cottonseed is a powerful stimulator of HuR gene expression in mouse macrophages, whose protein product is important for RNA stability and involved in the progression of rheumatoid arthritis, diabetes mellitus and some inflammatory diseases.

Technical Abstract: Human antigen R (HuR) stabilizes cytokine mRNAs and plays an important role in tumorigenesis and inflammation. Plant extracts and compounds that can regulate HuR gene expression may have nutritional and therapeutic value, but little was done. This study evaluated the effect of cottonseed extracts, anti-nutritional gossypol and endotoxin lipopolysaccharides (LPS) on HuR gene expression in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of glanded and glandless cottonseed extracts, gossypol and LPS for 2, 8 and 24 h. qPCR assay showed that cottonseed extracts and LPS had minor effect on HuR gene expression. However, gossypol increased HuR mRNA levels 16 fold in cells treated for 24 h. Immunoblotting confirmed that gossypol also increased HuR protein in macrophages. These results were the first to show that gossypol is a strong stimulator of HuR gene expression.