Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.

OBJECTIVE: To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism. METHODS: ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1ß, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1ß, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB. RESULTS: Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation. CONCLUSIONS: Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.

Characteristics of the cellular immune response in HIV/HCV patients with hemophilia during peginterferon/ribavirin therapy in southern China.

OBJECTIVE: The objectives of the study are to characterize the cellular immune response in hepatitis C virus (HCV) genotype 1 and HIV co-infected patients with hemophilia in southern China during treatment with interferon and ribavirin and to study its correlation with the virologic response (VR). Thirty-six HCV genotype 1 and HIV co-infected patients with hemophilia in southern China were enrolled into the study. Using an ELISpot assay, HCV antigen-specific interferon (IFN) γ, interleukin (IL) 2, IL-4, and IL-10 secreting cells were measured in peripheral blood mononuclear cells. Single nucleotide polymorphisms of IL28B were determined, and immunological, virologic, and clinical variables were collected to identify factors associated with HCV-sustained VR (SVR) at week 72 after treatment. At baseline, there were no significant differences in IFN-γ and IL-2 mediated immune responses in subjects with VR versus non-responders. Higher IL-10 specific responses to NS3 were observed in VR patients. Subjects who had significant decreases in IL-10 responses at week 72 compared with baseline for NS3 and NS5 were more likely to be VR. In SVR, IL-2 production decreased moderately, and the levels of IL-4 were low throughout. The main correlation for SVR in genotype-l infected subjects was sustained HCV-specific IFN-γ responses through the whole 72-week period. In subjects with HIV and HCV co-infection combined with hemophilia, IL28B genotype CC, a decrease in HCV specific IL-l0 and IL-2 responses, and the maintenance of IFN-γ responses during treatment were associated with a 12- or 72-week VR.