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Activation of Nlrp3 inflammasomes in Mouse Hepatic Stellate Cells during Schistosoma J. Infection
Author(s) -
Meng Nan,
Xia Min,
Li PinLan,
Tang WangXian
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1024.1
Subject(s) - inflammasome , schistosoma , hepatic stellate cell , inflammation , chemistry , schistosoma mansoni , biology , immunology , microbiology and biotechnology , schistosomiasis , endocrinology , helminths
Despite many studies, the molecular mechanisms initiating local inflammatory response and liver fibrosis during Schistosoma J. infection remain poorly understood. The present study hypothesized that NOD‐like receptor family, pyrin domain containing 3 (Nlrp3) inflammasomes serve as an intracellular machinery in hepatic stellate cells (HSCs) to turn on the inflammatory response and thereby instigate liver fibrosis during such infection. We first demonstrated that in mice infected with Schistosoma J . for 6 weeks liver exhibited increased IL‐1β level and collagen deposition at the periphery of the eosinophilic granuloma with Schistosoma J. eggs. When mice were administrated caspase‐1 inhibitor YVAD prior to and after Schistosoma J . infection, both increase in IL‐1β level and collagen deposition in liver were substantially attenuated. Using isolated, cultured mouse HSCs, we further explored the mechanism by which soluble egg antigen (SEA) from Schistosoma J. activates Nlrp3 inflammasomes. It was confirmed that SEA induced the formation of Nlrp3 inflammasomes, as shown by fluorescence confocal microscopy and thereby increased caspase‐1 activity and IL‐1β release from HSCs. All these changes related to Nlrp3 inflammasome formation and activation were found to be blocked by YVAD. In addition, the cathepsin B inhibitor, Ca‐074Me or antioxidant N‐acetyl‐L‐cysteine (NAC), but not the potassium channel blocker, glibenclamide (GLY) were also found to inhibit SEA‐induced Nlrp3 inflammasome formation and activation. These results suggest that Schistosoma J. infection may result in local inflammation by activation of Nlrp3 inflammasome in HSCs through its egg antigen stimulation and that activation of Nlrp3 inflammasomes in HSCs is associated with both redox regulation and lysosomal dysfunction, but not related to potassium channel activation.