Neutralization of Interleukin-17 Attenuates Cholestatic Liver Fibrosis in Mice.
Anti-inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. IL-17 is critical in inflammation, but the role of IL-17 in liver fibrosis has not yet been elucidated. In this study, we investigate the role of IL-17 on bile duct ligation-induced liver injury and fibrosis in C57BL/6 mice. Animals were sacrificed at designated times, and serum and liver tissues were collected for analysis of liver function and serum IL-6, IL-1β, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-β (TGF-β) levels. IL-17 blockade with anti-IL-17A mAb significantly improved liver function and decreased hepatocellular necrosis, pro-inflammatory cytokines, neutrophils and macrophages influx. Furthermore, CD3 + and CD8 + lymphocytes, neutrophils and macrophages were found to express IL-17, and neutrophils are the principal IL-17-producing cells after BDL-induced liver injury. These data indicated that IL-17 signal contributes to the pathogenesis of cholestatic liver injury and blocked of IL-17 could potentially benefit patients with cholestatic liver disease.
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
S
S
Zhang
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
D
D
Huang
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
J
J
Weng
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
Y
Y
Huang
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
S
S
Liu
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
Q
Q
Zhang
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
N
N
Li
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
M
M
Wen
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
G
G
Zhu
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
F
F
Lin
Department of Hepatopancreatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou Digestive Disease Center, Guangzhou, 510180, China.
W
W
Gu
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001652:Bile Ducts; D002779:Cholestasis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008026:Ligation; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D012333:RNA, Messenger