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http://dx.doi.org/10.4110/in.2012.12.4.148

Calcium/Calmodulin-Dependent Protein Kinase is Involved in the Release of High Mobility Group Box 1 Via the Interferon-${\beta}$ Signaling Pathway  

Ma, Lijuan (Department of Pathology, Hallym University College of Medicine)
Kim, Seon-Ju (Department of Pathology, Hallym University College of Medicine)
Oh, Kwon-Ik (Department of Pathology, Hallym University College of Medicine)
Publication Information
IMMUNE NETWORK / v.12, no.4, 2012 , pp. 148-154 More about this Journal
Abstract
Previously, we have reported that high mobility group box 1 (HMGB1), a proinflammatory mediator in sepsis, is released via the IFN-${\beta}$-mediated JAK/STAT pathway. However, detailed mechanisms are still unclear. In this study, we dissected upstream signaling pathways of HMGB1 release using various molecular biology methods. Here, we found that calcium/calmodulin-dependent protein kinase (CaM kinase, CaMK) is involved in HMGB1 release by regulating IFN-${\beta}$ production. CaMK inhibitor, STO609, treatment inhibits LPS-induced IFN-${\beta}$ production, which is correlated with the phosphorylation of interferon regulatory factor 3 (IRF3). Additionally, we show that CaMK-I plays a major role in IFN-${\beta}$ production although other CaMK members also seem to contribute to this event. Furthermore, the CaMK inhibitor treatment reduced IFN-${\beta}$ production in a murine endotoxemia. Our results suggest CaMKs contribute to HMGB1 release by enhancing IFN-${\beta}$ production in sepsis.
Keywords
Endotoxin shock; Cytokines; Inflammation; Signal transduction;
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