Dexamethasone inhibits NF‑кBp65 and HMGB1 expression in the pancreas of rats with severe acute pancreatitis

Abstract

Severe acute pancreatitis (SAP) starts as a local inflammation of pancreatic tissue that induces the development of multiple extra-pancreatic organ dysfunction; however, the underlying mechanisms remain unclear. The present study was designed to evaluate the effect of dexamethasone (DXM) on pancreatic damage and to investigate the role of high-mobility group box-1 (HMGB1) and nuclear factor-κB (NF-κBp65) in the development of SAP in animal and cell models. For the in vivo experiment, 35 Sprague-Dawley rats were randomly assigned to three groups: The sham-operation control group, the SAP group and the DXM treatment group. Histological analysis revealed that, when DXM was infused into SAP rats, edema formation and structural alterations with necrosis were reduced, and the number of apoptotic cells was markedly reduced. In addition, compared with the SAP group, the expression level of HMGB1 was significantly decreased in the nucleus and the expression level of NF-κBp65 was significantly decreased in the cytoplasm from rats treated with DXM. In vitro, DXM was able to suppress the apoptosis and cell death induced by caerulein (CAE), and DXM could suppress the expression of NF-κBp65 and HMGB1 induced by CAE, as demonstrated by western blotting and immunofluorescence analysis. Therefore, these results provide an experimental basis for investigating the underlying therapeutic mechanisms of DXM treatment for SAP.

Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

“…Steroids induce a reduction of NET formation in in vitro and vivo models [ 211 ]. Steroids also reduce the release of HMGB1 and its interaction with TLR4 [ 212 ] and modulate autophagy, inhibiting apoptosis and enhancing regulatory autophagosomes [ 212 , 213 ].…”

“…Steroids induce a reduction of NET formation in in vitro and vivo models [211]. Steroids also reduce the release of HMGB1 and its interaction with TLR4 [212] and modulate autophagy, inhibiting apoptosis and enhancing regulatory autophagosomes [212,213]. However, in SARS-CoV-2 infection, steroid treatment has not shown clear results in the literature and there is no indication statement.…”

miR‑9 alleviated the inflammatory response and apoptosis in caerulein‑induced acute pancreatitis by regulating FGF10 and the NF‑κB signaling pathway

“…NF-κB is comprised of p50 and p65 subunits and is activated by p65, which may promote the secretion of the inflammatory cytokines IL-1β, IL-6 and TNF-α (37,38). Furthermore, the NF-κB pathway has been associated with cell apoptosis in AP (39,40). The results of the current study demonstrated that caerulein led to the activation of NF-κB signaling in AR42J cells by decreasing IKBα and increasing p50 and p65, indicating that NF-κB pathway activation was involved in AP progression.…”

Serum microRNAs as novel biomarkers for early prediction of disease severity in patients with acute pancreatitis

“…MiR-19a, belonging to the cluster mir-17-92, has been proved to be regulated by the NF-κB p65 subunit and has a positive effect on NF-κB signaling [16,17]. NF-κB plays a key role in the pathogenesis of AP [18], suggesting that miR-19a is related to the initiation and cascade of inflammation in AP. Besides, using TargetScan, miR-19a was found to potentially regulate some genes related with inflammatory cascade, such as serum/glucocorticoid regulated kinase 1.…”