Boric acid inhibits LPS-induced TNF-alpha formation through a thiol-dependent mechanism in THP-1 cells.

Abstract

Oxidative stress plays an important role during inflammatory diseases and antioxidant administration to diminish oxidative stress may arrest inflammatory processes. Boron has been implicated to modulate certain inflammatory mediators and regulate inflammatory processes. Here we investigated the role of the tripeptide glutathione (GSH) in modulating the effects of boric acid (BA) on lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) formation in THP-1 monocytes. Interestingly, we found that BA had no significant effects on both TNF-alpha production and intracellular GSH contents, whereas it could inhibit LPS-induced TNF-alpha formation and ameliorated the d,l-buthionine-S,R-sulfoximine (BSO)-induced GSH depletion. Twenty-four hour incubation with BSO induced a decrease of the intracellular GSH and an increase of TNF-alpha. Treatment with N-acetyl-l-cysteine (NAC) did not significantly increase intracellular content of GSH but significantly reduced the secretion of TNF-alpha. BSO-pretreatment for 24h enhanced the LPS-induced secretion and mRNA expression of TNF-alpha further. BA inhibited LPS-stimulated TNF-alpha formation was also seen after GSH depletion by BSO. These results indicate that BA may have anti-inflammatory effect in the LPS-stimulated inflammation and the effect of BA on TNF-alpha secretion may be induced via a thiol-dependent mechanism.

• Authors: Jun Cao, Liping Jiang, Xiaomei Zhang, Xiaofeng Yao, Chengyan Geng, Xiangxin Xue, Laifu Zhong
• Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (J Trace Elem Med Biol) Vol. 22 Issue 3 Pg. 189-95 ( 2008) ISSN: 0946-672X [Print] Germany
• PMID: 18755394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Boric Acids
• Lipopolysaccharides
• RNA, Messenger
• Sulfhydryl Compounds
• Tumor Necrosis Factor-alpha
• Buthionine Sulfoximine
• Glutathione
• boric acid
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Boric Acids (pharmacology)
• Buthionine Sulfoximine (pharmacology)
• Cell Line
• Gene Expression Regulation (drug effects)
• Glutathione (metabolism)
• Humans
• Lipopolysaccharides (pharmacology)
• Monocytes (drug effects, metabolism)
• RNA, Messenger (genetics)
• Sulfhydryl Compounds (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis, genetics, metabolism)