title: Calcium/Calmodulin-Dependent Protein Kinase is Involved in the Release of High Mobility Group Box 1 Via the Interferon-β Signaling Pathway.
abstract: Previously, we have reported that high mobility group box 1 (HMGB1), a proinflammatory mediator in sepsis, is released via the IFN-β-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-β production. CaMK inhibitor, STO609, treatment inhibits LPS-induced IFN-β 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-β production although other CaMK members also seem to contribute to this event. Furthermore, the CaMK inhibitor treatment reduced IFN-β production in a murine endotoxemia. Our results suggest CaMKs contribute to HMGB1 release by enhancing IFN-β production in sepsis.
authors.affiliation: Department of Pathology, Hallym University College of Medicine, Chuncheon 200-702, Korea.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Ma
authors.forename: Seon-Ju
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kwon Ik
authors.initials: KI
authors.lastname: Oh
keywords: Cytokines; Endotoxin shock; Inflammation; Signal transduction