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Interleukin-17A Plays a Pivotal Role in Chemically Induced Hepatocellular Carcinoma in Mice
- Source :
- Digestive diseases and sciences. 61(2)
- Publication Year :
- 2015
-
Abstract
- The aim of the present study was to investigate the role of interleukin (IL)-17A in the initiation and progression of hepatocellular carcinoma. IL-17A deficient (KO) and wild-type (WT) mice were intraperitoneal injected with diethyl nitrosamine (DEN) to induce hepatocellular carcinoma, and the incidence of tumours was assessed 38 weeks later. In order to investigate the effects of DEN on hepatocytes in the acute phase of DEN administration, DEN-treated mice were sacrificed at designated time points. Serum and liver tissues were harvested for further analyses. The tumor incidence was approximately 65 % in WT mice, but was significantly lower (by 20 %) in KO mice. The number of tumours was also less in KO mice. Serum ALT levels increased in WT mice 7 days after the administration of DEN, but were significantly lower in KO mice. Furthermore, the number of neutrophils and Kupffer cells, and the expression of TNF-α and IL-6 were reduced in KO mice. The intrahepatic expression of the oxidative DNA damage marker 8-OHdG and lipid oxidative marker 4-HNE was markedly increased in WT mice, but was significantly lower in KO mice. In addition, the increase of cell proliferation, as assessed by Ki-67 immunohistochemistry, in WT mice was significantly reduced in KO mice. These results demonstrated that IL-17A plays a pivotal role in chemically induced hepatic carcinogenesis, which is most likely through inflammation-initiated oxidative DNA damage and cell proliferation.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Pathology
Carcinoma, Hepatocellular
Physiology
DNA damage
medicine.disease_cause
03 medical and health sciences
Mice
Internal medicine
medicine
Animals
Diethylnitrosamine
Interleukin 6
Cell Proliferation
Mice, Knockout
biology
Chemistry
Cell growth
Interleukin-6
Tumor Necrosis Factor-alpha
Interleukin-17
Liver Neoplasms
Gastroenterology
Interleukin
Deoxyguanosine
medicine.disease
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Oxidative Stress
030104 developmental biology
Endocrinology
8-Hydroxy-2'-Deoxyguanosine
Hepatocellular carcinoma
biology.protein
Tumor necrosis factor alpha
Interleukin 17
Oxidative stress
DNA Damage
Subjects
Details
- ISSN :
- 15732568
- Volume :
- 61
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Digestive diseases and sciences
- Accession number :
- edsair.doi.dedup.....6dbe85390acee334d404088abcfa7c0d