Abstract
Staphylococcal enterotoxin B (SEB) has been documented to be implicated in the pathogenesis of liver injury in the experimental models of hepatitis. However, the underlying mechanism of SEB-induced acute liver injury (ALI) remains to be further explored. In our study, we explored the therapeutic effectiveness of berberine (BBR), a natural isoquinoline alkaloid, in the SEB-induced ALI. In our study, we found that injection of SEB into d-galactosamine (d-gal)-sensitized mice induced ALI, as demonstrated by an increase of levels of alanine aminotransferase and aspartate aminotransferase, massive infiltration of immune cells into the liver, and pro-inflammatory cytokine release. However, intragastric administration of BBR attenuated SEB-induced ALI in mice. Meanwhile, we discovered that BBR treatment suppressed activation of splenocytes and pro-inflammatory cytokine release in SEB-stimulated splenocytes. Moreover, mechanistic analyses demonstrated that BBR was effective at inhibiting the expression of class I HDAC, but not class II, in SEB-stimulated splenocytes. Furthermore, trichostatin A, a standard HDAC inhibitor, alleviated activation of splenocytes and pro-inflammatory cytokine release in SEB-stimulated splenocytes. Taken together, we inferred from these results that BBR attenuated SEB-mediated ALI through repressing the class I HDAC enzyme, suggesting that BBR may constitute a novel therapeutic modality to prevent SEB-mediated inflammation and ALI.
Highlights
Staphylococcus aureus (S. aureus), a ubiquitous Grampositive opportunistic pathogen that can be found in 20% of the general human population, has emerged as a major cause of nosocomial infections and community acquired diseases (Pinchuk et al 2010)
BBR attenuated staphylococcal enterotoxin B (SEB)‐induced acute liver injury (ALI) in mice To address the effect of BBR on SEB-induced ALI, these mice were initially sensitized by giving them an intraperitoneal injection of 20 mg of d-galactosamine (d-gal) in 100 μl phosphate-buffered saline (PBS) 30 min prior to SEB injection, as previously described (Hegde et al 2011)
We further examined the effects of BBR on the expressions of class I and major histocompatibility complex class II (II) histone deacetylases (HDACs) enzymes and qRT-PCR analyses showed that treatment with SEB significantly upregulated the expressions of class I HDAC (HDAC1, HDAC2, HDAC3, and HDAC8) and downregulated the expressions of class II HDAC (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10) in comparison to unstimulated cells (Fig. 4b, c)
Summary
Staphylococcus aureus (S. aureus), a ubiquitous Grampositive opportunistic pathogen that can be found in 20% of the general human population, has emerged as a major cause of nosocomial infections and community acquired diseases (Pinchuk et al 2010). Its pathogenicity can be attributed to a number of virulence factors including staphylococcal enterotoxin B (SEB) (Foster 2004). Du et al AMB Expr (2018) 8:158 extracts have multiple beneficial pharmacological effects including anti-inflammation (Bae and Cheon 2016), antioxidant (Jung et al 2009), anti-bacterial (Yu et al 2005), immunoregulative (Kim et al 2003), and hepatoprotective (Ye et al 2009). Extensive researches have documented the inhibitory effects of BBR on chemically induced cytotoxicity and oxidative stress in the liver (Hwang et al 2002; Zhang et al 2008). The hepatoprotective effect of BBR has been characterized, the roles of BBR in SEB-induced acute liver injury (ALI) are still undefined
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