title: 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.affiliation: Department of Toxicology, Dalian Medical University, 9 Lushunnan Road, Dalian 116044, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Yao
authors.forename: Chengyan
authors.initials: C
authors.lastname: Geng
authors.forename: Xiangxin
authors.initials: X
authors.lastname: Xue
authors.forename: Laifu
authors.initials: L
authors.lastname: Zhong