title: Mainstream cigarette smoke accelerates the progression of nonalcoholic steatohepatitis by modulating Kupffer cell-mediated hepatocellular apoptosis in adolescent mice.
abstract: Cigarette smoking in adolescents is considered to be a major cause of preventable morbidity and mortality. The purpose of this study is to investigate the role of mainstream cigarette smoke (MSCS) on the progression of nonalcoholic steatohepatitis in adolescents. Three-week-old C57BL/6 mice were fed either a methionine and choline-deficient plus high fat (MCDHF) diet for 6 weeks. Each group was exposed to MSCS (300, 600 ug/L) or fresh air for 2h per day during the first 3 weeks of MCDHF diet feeding. MSCS increased MCDHF diet-induced NASH by increasing serum ALT/AST levels, steatosis, inflammation, and fibrosis. Furthermore, MSCS was associated with the degree of oxidative stress and hepatocellular apoptosis in NASH mice, but not prominent in controls. In vitro, cigarette smoke extract (CSE) activated Kupffer cells (KCs) to release inflammatory cytokines and oxidative stress, which induced hepatocellular apoptosis. In conclusion, MSCS exposure accelerates the progression and severity of NASH by modulating KC-mediated hepatocellular apoptosis. Our results support the regulation of CS in adolescents with steatohepatitis.
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Surim
authors.initials: S
authors.lastname: Park
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Yun
authors.affiliation: Inhalation Toxicology Center, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, Republic of Korea.
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Choi
authors.affiliation: Inhalation Toxicology Center, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, Republic of Korea.
authors.forename: Sang-Hyub
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea.
authors.forename: Chae Woong
authors.initials: CW
authors.lastname: Lim
authors.affiliation: Inhalation Toxicology Center, Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, Republic of Korea. Electronic address: khleekit@gmail.com.
authors.forename: Kyuhong
authors.initials: K
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute and Laboratory of Pathology (BK21 Plus Program), College of Veterinary Medicine, Chonbuk National University, Iksan, Republic of Korea. Electronic address: bskims@jbnu.ac.kr.
authors.forename: Bumseok
authors.initials: B
authors.lastname: Kim
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D002796:Choline Deficiency / Q000150:complications; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000172:deficiency; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D019899:Paracrine Communication; D012720:Severity of Illness Index; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D012906:Smoke; D008715:Methionine
keywords: Hepatocellular apoptosis; Kupffer cell; Mainstream cigarette smoke (MSCS); Nonalcoholic steatohepatitis