Calcium/Calmodulin-Dependent Protein Kinase is Involved in the Release of High Mobility Group Box 1 Via the Interferon-beta Signaling Pathway
Immune Network
;
: 148-154, 2012.
Article
in English
| WPRIM
| ID: wpr-192565
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Phosphotransferases
/
Protein Kinases
/
Benzimidazoles
/
Signal Transduction
/
Cytokines
/
Interferon-beta
/
Sepsis
/
Endotoxemia
/
HMGB1 Protein
Language:
English
Journal:
Immune Network
Year:
2012
Type:
Article
Similar
MEDLINE
...
LILACS
LIS