Involvement of M3 cholinergic receptor signal transduction pathway in regulation of the expression of chemokine MOB-1, MCP-1 genes in pancreatic acinar cells.
- Author:
Hai ZHENG
1
;
Daoda CHEN
;
Jinghui ZHANG
;
Yuan TIAN
Author Information
1. Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
- Publication Type:Journal Article
- MeSH:
Adaptor Proteins, Signal Transducing;
Carbachol;
pharmacology;
Carrier Proteins;
biosynthesis;
genetics;
Chemokine CCL2;
biosynthesis;
genetics;
Chemokines;
biosynthesis;
genetics;
Humans;
NF-kappa B;
biosynthesis;
genetics;
Pancreas, Exocrine;
metabolism;
Pancreatitis;
etiology;
RNA, Messenger;
biosynthesis;
genetics;
Receptor, Muscarinic M3;
agonists;
physiology;
Signal Transduction
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2004;24(2):140-157
- CountryChina
- Language:English
-
Abstract:
Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-kappaB and the expression of chemokine MOB-1, MCP-lgenes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-kappaB was monitored by using electrophoretic mobility shift assay. The results showed that as compared with control group, M3 cholinergic receptor agonist (10(-3) mol/L, 10(-4) mol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10(-3) mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-kappaB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10(-3) mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10(-5) mol/L atropine) or NF-kappaB inhibitor (10(-2) mol/L PDTC) could obviously inhibit the activation of NF-kappaB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P<0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-lgenes in pancreatic acinar cells in vitro through the activation of NF-kappaB.
