Rabbit Anti-Human HMGB1 (a.a. 1-215) Polyclonal antibody

Inflammasomes are an important innate immune host defense against intracellular microbial infection. Activation of inflammasomes by microbial or host ligands results in cleavage of caspase-1 (canonical pathway) or caspase-11 (noncanonical pathway), release of interleukin (IL)-1 beta, IL-18, high mobility group box 1 (HMGB1), and inflammatory cell death known as pyroptosis.Ehrlichiaare obligate, intracellular, gram-negative bacteria that lack lipopolysaccharide but cause potentially life-threatening monocytic ehrlichiosis in humans and mice that is characterized by liver injury followed by sepsis and multiorgan failure. Employing murine models of mild and fatal ehrlichiosis caused by infection with mildly and highly virulentEhrlichia muris(EM) andIxodes ovatus Ehrlichia(IOE), respectively, we have previously shown that IOE infection triggers type I interferon (IFN-I) response and deleterious caspase-11 activation in liver tissues, which promotes liver injury and sepsis. In this study, we examined the contribution of IFN-I signaling in hepatocytes (HCs) toEhrlichia-induced liver injury. Compared to EM infection, we found that IOE enter and replicatein vitrocultured primary murine HCs and induce secretion of IFN beta and several chemokines, including regulated upon activation, normal T-cell expressed, and secreted (RANTES), monocyte chemoattractant protein 1 (MCP1), monokine induced by gamma (MIG)/chemokine (C-X-C motif) ligand 9 (CXCL9), macrophage inflammatory protein 1 alpha (MIP1 alpha), keratinocyte-derived chemokine (KC), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Notably,in vitrostimulation of uninfected andEhrlichia-infected HCs with recombinant IFN beta triggered activation of caspase-1/11, cytosolic translocation of HMGB1, and enhanced autophagy and intracellular bacterial replication. Secretion of HMGB1 by IOE-infected HCs was dependent on caspase-11. Primary HCs from IOE- but not EM-infected mice also expressed active caspase-1/11.Conclusion:HC-specific IFN-I signaling may exacerbate liver pathology during infection with obligate intracellularEhrlichiaby promoting bacterial replication and detrimental caspase-11-mediated inflammasome activation.

Preterm birth (PTB) is the primary cause of neonatal mortality worldwide. Infection and inflammation are considered to be the primary causes of PTB. Cervical remodeling is an important step in the process of preterm delivery, and the destruction of the cervical epithelial barrier and inflammation are important triggers of cervical remodeling. The aim of the present study was to determine the effect and underlying mechanism of microRNA (miR)-199a-3p/high-mobility group box 1 protein (HMGB1) signaling in cervical epithelial inflammation in PTB. The results of this study revealed that miR-199a-3p was significantly decreased in cervical epithelial tissue samples from patients in both the preterm labor and preterm premature rupture of membrane groups. This decrease was also observed in tissue samples from a lipopolysaccharide (LPS)-induced PTB mouse model and in LPS-induced ectocervical and endocervical cells. Whereas, the expression of HMGB1 and toll-like receptor 4 (TLR4) was significantly increased, which was associated with the upregulation of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha expression. Furthermore, overexpression of miR-199a-3p significantly suppressed the expression and activation of HMGB1 and TLR4/NF-kappa B signaling, and decreased the levels of IL-1 beta and TNF-alpha in vitro and in vivo. Additionally, overexpression of HMGB1 and/or TLR4 reversed the anti-inflammatory effects of miR-199a-3p mimics in vitro and in vivo. These results indicate that miR-199a-3p acts as a negative inflammatory regulator in PTB by targeting HMGB1 to regulate the TLR4/NF-kappa B pathway.