Interleukin-6 secreted by bipotential murine oval liver stem cells induces apoptosis of activated hepatic stellate cells by activating NF-κB-inducible nitric oxide synthase signaling.
Liver fibrosis is now well recognized as the causative factor for increased mortality from complications associated with liver pathologies. Activated hepatic stellate cells (HSCs) play a critical role in the progression of liver fibrosis. Therefore, targeting these activated HSCs to prevent and (or) treat liver disease is a worthwhile approach to explore. In the present in vitro study, we investigated the use of bipotential murine oval liver cells (BMOL) in regulating the functions of activated HSCs to prevent progression of liver fibrosis. We used a conditioned medium-based approach to study the effect of BMOL cells on activated HSC survival and function. Our data showed that BMOL cells block the contraction of activated HSCs by inducing apoptosis of these cells. We demonstrated that BMOL cells secrete soluble factors, such as interleukin-6 (IL-6), which induced apoptosis of activated HSCs. Using both pharmacological and molecular inhibitor approaches, we further identified that IL-6-mediated activation of NF-κB-iNOS-NO-ROS signaling in activated HSCs plays a critical role in BMOL-cell-mediated apoptosis of activated HSCs. Thus, the present study provides an alternative cell-based therapeutic approach to treat liver fibrosis.
a Life Sciences Division, AU-KBC Research Centre, Anna University, Chennai, India.
Palanivel
P
Gajalakshmi
b Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
Syamantak
S
Majumder
c Centre for Medical Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Australia.
Cornelia S
CS
Viebahn
a Life Sciences Division, AU-KBC Research Centre, Anna University, Chennai, India.
Akila
A
Swaminathan
c Centre for Medical Research, Harry Perkins Institute of Medical Research, University of Western Australia, Nedlands, Australia.
George C
GC
Yeoh
a Life Sciences Division, AU-KBC Research Centre, Anna University, Chennai, India.|d Department of Biotechnology, Anna University, Chennai, India.
Suvro
S
Chatterjee
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
D000578:Amidines; D001152:Arsenicals; D001596:Benzylamines; D017077:Culture Media, Conditioned; D007093:Imidazoles; D015850:Interleukin-6; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011810:Quinoxalines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D000093242:Interleukin-6 Inhibitors; C471109:4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; C104820:N-(3-(aminomethyl)benzyl)acetamidine; C577686:interleukin-6, mouse; C029341:oxophenylarsine; C496317:Nos2 protein, mouse
IL-6; cellules de Kupffer; cellules souches hépatiques; fibrose hépatique; hepatic stellate cells; iNOS; liver fibrosis; liver stem cells