In addition, simvastatin effectively reduced the intestinal levels of tumor necrosis factor α, interleukin-6, high-mobility group box 1, and malondialdehyde and increased the activity of superoxide dismutase in rats with sepsis.
In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury.
Serum markers associated with the acute proinflammatory phase of sepsis (TNFα, IL-1β, and IL-6) rapidly increased and then progressively decreased during the 30-day period post-CLP, concomitant with a progressive increase in RAGE ligands (S100B, <i>N</i>ϵ-[carboxymethyl]lysine, HSP70, and HMGB1).
In this study, we deleted the murine <i>Gstp</i> gene cluster and found that GSTP significantly decreased the mortality of experimental sepsis and reduced related serum level of high mobility group box-1 protein (HMGB1).
High-mobility group box 1 (HMGB1), a danger-associated molecular pattern protein, is released during infection and contributes to the pathogenesis of sepsis.
Forced expression of CRBN in macrophage of KO mice suppressed activation of 5' adenosine monophosphate-activated protein kinase (AMPK) and HO-1 and augmented expression of TNF-α and HMGB1 as inhibition of AMPK by compound C. These studies demonstrate the contribution of CRBN expression to the pathogenesis of CLP-induced sepsis and peritoneal macrophage responses and suggest a novel therapeutic modality for polymicrobial sepsis.
The inhibition of exosomal microRNA-126 failed to block LPS-induced increase in HMGB1 and VCAM1 protein levels in HMVECs and negated the protective effect of exosomes on sepsis survival.
Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema.
Moreover, we suggested that miR-181a-5p may play a role in regulating DC responses to HMGB1 and serve as evidence indicating that novel therapies targeting miRNAs may be useful for treating immune dysfunction in the setting of sepsis.
Taken together, our data suggest that HMGB1 accumulation in the late phase of sepsis plays a specific role in the development of postsepsis immunosuppression and specifically affects neutrophil-dependent antibacterial defense mechanisms.
In addition, rTM administered prior to or after LPS suppressed the level of pro-inflammatory cytokine TNF-α in sera at 1-3 h after LPS injection, whereas only the administration of rTM after LPS suppressed the levels of HMGB1 and nucleosome (late-phase mediators of sepsis) (9-12 h) in sera after the LPS injection.