Activation of nuclear factor kappa B in the hepatic stellate cells of mice with schistosomiasis japonica
Authors: Dongmei Zhang
Guangbin Pu
Weiqing Pan
Xing He
Rui Tang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Schistosomiasis japonica; Hepatic stellate cells (HSCs); Nuclear factor kappa B (NF-Œ∫B); Inflammation; Fibrosis
Affiliations: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, China.

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-Œ∫B), a critical mediator of inflammatory responses, plays in schistosome-induced inflammation. We revealed that NF-Œ∫B 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-Œ∫B signaling (Ccl2, Ccl3 and Ccl5) were similarly elevated at early infection. TLR4 signaling, one of the strongest known inducers of NF-Œ∫B activation, seemed not activated in HSCs post-infection. Importantly, we found that levels of miR-146 (a known negative regulator of NF-Œ∫B signaling) in HSCs opposed those of NF-Œ∫B 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-Œ∫B 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-Œ∫B signaling or miR-146 expression may provide a novel method of treating hepatic schistosomiasis japonica. 

Retracted: No

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 December 2020 Correction found here: https: journals.plos.org plosone article?id=10.1371 journal.pone.0243667 From the Correction notice:  After this article [1] was published, it was noted that the p65 (cytoplasm) and p65 (total) panels in Fig 4A report the same data. The authors apologize for the error and noted that the wrong data were included in the p65 (cytoplasm) panel. An updated Fig 4 is provided here and the underlying data for this figure are in S1 File. The image issues do not affect the quantitative results in Fig 4B and 4C.  The Results section text discussing Fig 4Au20134C are revised as follows: Our results revealed that NF-u03baB activity (presented as the ratio of nuclear p65 to cytoplasmic p65) in HSCs increased significantly by 32 days post-infection (dpi), but returned to pre-infection levels by 42 dpi (Fig 4A and 4B). In contrast, expression levels of total p65 increased between 0 and 32 dpi, and then were down-regulated by 42 dpi to levels below those observed at baseline (Fig 4A and 4C). The original flow cytometry data files underlying Fig 3A are no longer available. The underlying data to support other results in the article are provided in S2-S4 Files. It took six years between my report of this duplication in August 2014 to this correction. I thank the authors and the PLOS editorial team for correcting this error. ,