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Young Joo Oh, Ju Ho Youn, Jeon Soo Shin, HMGB1 secretion is regulated by protein kinase C (89.26), The Journal of Immunology, Volume 178, Issue 1_Supplement, April 2007, Pages S153–S154, https://doi.org/10.4049/jimmunol.178.Supp.89.26
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Abstract
High mobility group box-1 protein (HMGB1) is secreted from activated monocytes/macrophages and known as a key late mediator of sepsis, so the regulation of secretion is important to control the sepsis. Phosphorylation of HMGB1 is one of major secretion pathways in our previous report. To investigate the phosphorylation-related pathway of HMGB1, LPS-induced HMGB1 secretion was observed with various inhibitors in RAW264.7 cells. Wortmannin and LY294002 inhibited HMGB1 secretion, suggesting the involvement of phosphoinositide 3-kinase (PI3K). Akt inhibitor IV and rapamycin failed to inhibit HMGB1 secretion, suggesting no relevance of Akt-mTOR axis pathway. In contrast, protein kinase C (PKC) inhibitor Gö6983 could inhibit HMGB1 secretion. And we confirmed that HMGB1 was directly phosphorylated by PKC but not by casein kinase II or cdc2 in in vitro kinase assay using autoradiography and □-scintillation counting. When RAW264.6 cells were pre-treated with JNK inhibitor, LPS-induced HMGB1 secretion was decreased but not by PD 98059 and SB 203580, p42/44 and p38 pathway inhibitors respectively. These results suggesting that PKC is effector kinase for HMGB1 phosphorylation for secretion and PI3K may act in concert to control of HMGB1 secretion via a pathway independent manner of p42/44 and p38 MAPK. Which specific isoform of PKC is involved in HMGB1 phosphorylation is now under investigation.
