Caerulin-induced pro-inflammatory response in macrophages requires TRAF3-p38 signaling activation.
Biochem Biophys Res Commun
; 494(1-2): 358-364, 2017 12 09.
Article
in En
| MEDLINE
| ID: mdl-28988112
ABSTRACT
Acute pancreatitis is a common threat to human health. Caerulin provokes severe inflammations, causing injuries to surrounding pancreatic cells. TNF receptor-associated factor 3 (TRAF3) is a highly versatile regulator of immune response. The current study aims to understand the potential effect of TRAF3 on caerulin-induced pro-inflammatory responses. In the primary-cultured mouse bone marrow-derived macrophages (BMDMs), caerulin induced TRAF3 protein stabilization, which formed a complex with mitogen-activated protein kinase kinase 3 (MKK3) to mediate downstream p38 activation. Lentiviral shRNA-mediated TRAF3 stable knockdown significantly attenuated caerulin-induced MKK3-p38 activation and production of several key pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-17. Remarkably, TRAF3 knockdown in caerulin-stimulated BMDMs also alleviated cytotoxicity to Panc02 and primary mouse pancreatic cells. Thus, TRAF3 is required for caerulin-induced p38 activation and macrophage-mediated pro-inflammatory responses. TRAF3 expression in macrophages could be a novel therapeutic target protein for the treatment of acute pancreatitis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ceruletide
/
Signal Transduction
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P38 Mitogen-Activated Protein Kinases
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TNF Receptor-Associated Factor 3
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Epithelial Cells
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Macrophages
Limits:
Animals
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2017
Type:
Article
Affiliation country:
China