title: Activation of nuclear factor kappa B in the hepatic stellate cells of mice with schistosomiasis japonica.
abstract: Schistosomiasis japonica is a serious tropical parasitic disease in humans, which causes inflammation and fibrosis of the liver. Hepatic stellate cells (HSCs) are known to play an important role in schistosome-induced fibrosis, but their role in schistosome-induced inflammation is still largely unknown. Here, we use a murine model of schistosomiasis japonica to investigate the role that nuclear factor kappa B (NF-κB), a critical mediator of inflammatory responses, plays in schistosome-induced inflammation. We revealed that NF-κB was significantly activated in HSCs at the early stage of infection, but not at later stages. We also show that the expression levels of several chemokines regulated by NF-κB signaling (Ccl2, Ccl3 and Ccl5) were similarly elevated at early infection. TLR4 signaling, one of the strongest known inducers of NF-κB activation, seemed not activated in HSCs post-infection. Importantly, we found that levels of miR-146 (a known negative regulator of NF-κB signaling) in HSCs opposed those of NF-κB signaling, elevating at later stage of infection. These results indicate that HSCs might play an important role in the progression of hepatic schistosomiasis japonica by linking liver inflammation to fibrosis via NF-κB signaling. Moreover, our work suggests that miR-146 appeared to regulate this process. These findings are significant and imply that manipulating the function of HSCs by targeting either NF-κB signaling or miR-146 expression may provide a novel method of treating hepatic schistosomiasis japonica.
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, China.
authors.forename: Guangbin
authors.initials: G
authors.lastname: Pu
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D012554:Schistosomiasis japonica / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D016328:NF-kappa B; D051197:Toll-Like Receptor 4