ABSTRACT
BACKGROUND: Neutrophils infiltrate the livers of patients with nonalcoholic steatohepatitis (NASH). Human neutrophil peptides (HNPs) induce cytokine and chemokine production under inflammatory conditions, which may contribute to the progression of NASH. In this study, we focused on the effects of HNP-1 on hepatic steatosis and fibrosis in a mouse model of NASH induced by a choline-deficient, L-amino acid-defined (CDAA) diet. MATERIALS & METHODS: We generated transgenic mice expressing HNP-1 under the control of a ß-actin-based promoter. HNP-1 transgenic and wild-type C57BL/6N mice were fed a CDAA diet for 16 weeks to induce hepatic steatosis and fibrosis. Serological and histological features were examined, and the effects of HNP-1 on hepatic stellate cell lines were assessed. RESULTS: HNP-1 transgenic and wild-type mice fed the CDAA diet showed no significant differences in serum alanine aminotransferase levels or the degree of hepatic steatosis based on Oil red O staining and hepatic triglyceride content. In contrast, Sirius Red and Azan staining showed significantly more severe hepatic fibrosis in HNP-1 transgenic mice compared with wild-type mice. In addition, significantly more α-smooth muscle actin-positive hepatic stellate cells were observed in the transgenic mice than in the wild-type mice. Finally, the proliferation of the LI90 hepatic stellate cell line increased in response to HNP-1. CONCLUSION: Our data indicate that HNP-1 enhances hepatic fibrosis in fatty liver by inducing hepatic stellate cell proliferation. Thus, neutrophil-derived HNP-1 may contribute to the progression of NASH.
Subject(s)
Diet , Fatty Liver/metabolism , Liver Cirrhosis/metabolism , alpha-Defensins/metabolism , 2,2'-Dipyridyl/analogs & derivatives , Alanine Transaminase/blood , Amino Acids/metabolism , Animals , Azabicyclo Compounds , Azo Compounds , Cell Proliferation , Choline Deficiency , Hepatic Stellate Cells/physiology , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Non-alcoholic Fatty Liver DiseaseABSTRACT
A 59-year-old woman was admitted to our hospital because of a pancreatic mass lesion. Serum gamma-globulin and IgG4 levels were elevated to 2.2 g/dL and 1,310 mg/dL, respectively. Computed tomography examination revealed multiple low-density areas without enhancement by contrast in the pancreatic body and bilateral kidneys. Endoscopic retrograde cholangiopancreatography images demonstrated diffuse narrowing of the main pancreatic duct with an irregular wall from the body to the tail of the pancreas. Positron emission tomography examination revealed intense 18F-fluorodeoxyglucose uptake by the pancreas and kidneys. Accordingly, the patient was diagnosed as having IgG4-related autoimmune pancreatitis. In addition, the findings of a renal tissue specimen obtained by biopsy demonstrated IgG4-positive plasma cell infiltration in both abnormal mass lesions and normal regions by imaging, leading to the final diagnosis of IgG4-related sclerotic disease. The patient was treated with prednisolone (30 mg/day), and the size of the pancreatic and renal lesions markedly decreased four weeks later. We report here a rare case of IgG4-related autoimmune pancreatitis with multiple renal lesions, which were confirmed by renal biopsy.
