HMGB1 promotes the synthesis of pro-IL-1β and pro-IL-18 by activation of p38 MAPK and NF-κB through receptors for advanced glycation end-products in macrophages.
The high mobility group box-1 (HMGB1) protein and NALP3 inflammasome have been identified to play important roles in inflammation and cancer pathogenesis, but the relationships between the two and cancer remain unclear. The current study investigated the relationship between HMGB1 and the NALP3 inflammasome in THP-1 macrophages. HMGB1 was found unable to activate the NALP3 inflammasome and failed to induce the release of the IL-1β and IL-18 in THP-1 macrophages. HMGB1 was also found significantly enhanced the activity of ATP to induce IL-1β and IL-18 by the induction of increased expression of pro-IL-1β and pro-IL-18. This process was dependent on activation of RAGE, MAPK p38 and NF-κB signaling pathway. These results demonstrate that HMGB1 promotes the synthesis of pro-IL-1β and pro-IL-18 in THP-1 macrophages by the activation of p38 MAPK and NF-κB through RAGE. HMGB1 likely plays an important role in the first step of the release of the IL-1β and IL-18, preparing for other cytokines to induce excessive release of IL-1β and IL-18 which promote inflammation and cancer progression.
Institute of Integrated Traditional Medicine and Western Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Qiang
Q
He
Hong
H
You
Xin-Min
XM
Li
Tian-Hui
TH
Liu
Ping
P
Wang
Bao-En
BE
Wang
D000704:Analysis of Variance; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D024243:HMGB1 Protein / Q000494:pharmacology*; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis*; D053583:Interleukin-1beta / Q000096:biosynthesis*; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*
D002352:Carrier Proteins; D024243:HMGB1 Protein; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D048051:p38 Mitogen-Activated Protein Kinases