ABSTRACT
BACKGROUND AND AIMS: Neutrophil infiltration of the liver is a typical feature of alcoholic liver injury. Human neutrophil peptide (HNP)-1 is an antimicrobial peptide secreted by neutrophils. The aim of this study was to determine if HNP-1 affects ethanol-induced liver injury and to examine the mechanism of liver injury induced by HNP-1. METHODS: Transgenic (TG) mice expressing HNP-1 under the control of a ß-actin-based promoter were established. Ethanol was orally administered to HNP-1 TG or wild-type C57BL/6N (WT) mice. SK-Hep1 hepatocellular carcinoma cells were used to investigate the effect of HNP-1 on hepatocytes in vitro. RESULTS: After 24 weeks of ethanol intake, hepatic fibrosis and hepatocyte apoptosis were significantly more severe in TG mice than in WT mice. Levels of CD14, TLR4, and IL-6 in liver tissues were higher in TG mice than in WT mice. Apoptosis was accompanied by higher protein levels of caspase-3, caspase-8, and cleaved PARP in liver tissue. In addition, phosphorylated ASK1, ASK1, phosphorylated JNK, JNK1, JNK2, Bax, Bak and Bim were all more abundant in TG mice than in WT mice. In contrast, the level of anti-apoptotic Bcl2 in the liver was significantly lower in TG mice than in WT mice. Analysis of microRNAs in liver tissue showed that miR-34a-5p expression was significantly higher in TG mice than in WT mice. Furthermore, in the presence of ethanol, HNP-1 increased the apoptosis with the decreased level of Bcl2 in a concentration-dependent manner in vitro. CONCLUSIONS: HNP-1 secreted by neutrophils may exacerbate alcohol-induced hepatic fibrosis and hepatocyte apoptosis with a decrease in Bcl2 expression and an increase in miR-34a-5p expression.
Subject(s)
Apoptosis , Ethanol/toxicity , Hepatocytes/physiology , alpha-Defensins/physiology , Animals , Cell Line, Tumor , Endoplasmic Reticulum Stress , Hepatocytes/drug effects , Humans , Liver Cirrhosis, Alcoholic , Male , Mice, Transgenic , MicroRNAs/genetics , MicroRNAs/metabolism , Neutrophil Infiltration , Neutrophils/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolismABSTRACT
Infected hepatic cysts are very rare compared to simple liver cysts and abscesses. We treated a 77-year-old man with an infected hepatic cyst in the lateral segment caused by Edwardsiella tarda, which has not been previously reported as a pathogenic organism associated with infected hepatic cysts. Percutaneous drainage was temporarily effective, but infection recurred after the drainage tube was removed. We then inserted two drainage tubes into the cyst using an endoscopic ultrasonography (EUS)-guided technique, which was developed from EUS-guided fine needle aspiration (EUS-FNA). The internal drainage tube was a 7 Fr double pigtail stent, and the external tube was a 6 Fr nasobiliary drainage tube. Lavage through the external drainage tube was carried out for one week. The external drainage tube was discontinued when the patient's condition improved significantly. Sixteen days after tube insertion, he was discharged with the internal tube draining the hepatic cyst into the stomach. Fifteen months after EUS-guided drainage, CT examination showed no recurrence of the hepatic cyst. EUS-guided drainage is an effective treatment for infected hepatic cysts.