Calcium/Calmodulin-Dependent Protein Kinase is Involved in the Release of High Mobility Group Box 1 Via the Interferon-beta Signaling Pathway.
- Author:
Lijuan MA
1
;
Seon Ju KIM
;
Kwon Ik OH
Author Information
- Publication Type:Original Article
- Keywords: Endotoxin shock; Cytokines; Inflammation; Signal transduction
- MeSH: Benzimidazoles; Cytokines; Endotoxemia; HMGB1 Protein; Inflammation; Interferon Regulatory Factor-3; Interferon-beta; Molecular Biology; Naphthalimides; Phosphorylation; Phosphotransferases; Protein Kinases; Sepsis; Signal Transduction
- From:Immune Network 2012;12(4):148-154
- CountryRepublic of Korea
- Language:English
- 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.
