Effect of pioglitazone on inflammatory signaling pathways induced by pancreatitis-associated ascitic fluid in human monocytic cell line THP-1
10.3724/SP.J.1008.2012.01182
- Author:
Ping XU
1
Author Information
1. Department of Gastroenterology, Songjiang Branch, The First People's Hospital of Shanghai, Shanghai Jiaotong University
- Publication Type:Journal Article
- Keywords:
Monocytes;
NF-κB;
P38 mitogen-activated protein kinases;
Pancreatitis;
Pioglitazone
- From:
Academic Journal of Second Military Medical University
2012;33(11):1182-1185
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the inhibitory effect of pioglitazone on inflammatory signaling pathways induced by human pancreatitis-associated ascitic fluid (PAAF) in human monocytic cell line THP-1. Methods: PAAF was collected from patients with severe acute pancreatitis. The cultured THP-1 cells were divided into 4 groups: control group (C), PAAF group (A), PPARγ agonist pioglitazone group (P), and PPARγ antagonist GW9662 group (G). Cells in group A were stimulated with PAAF, those in group P were treated with 20 mol/L PPARγ agonist pioglitazone 2 h after stimulation with PAAF, and those in group G were treated with PPARγ antagonist GW9662, pioglitazone (30 min later) and PAAF(2 h later) in turn. After incubation for 12 h, TNF-α and IL-6 mRNA expression was measured by real-time PCR, and Western blotting analysis was used to examine the expression of the phospho-P38-mitogen-activated protein kinase (MAPK), nuclear transcription factor (NF-κB) P65 levels, and IκB Results: Compared with group C, TNF-α and IL-6 mRNA expression in group A was increased, NF-κB and P8MAPK protein levels were increased, and IκB protein level was decreased (P<0. 05). Compared with group A, TNF-α and IL-6 mRNA expression was decreased in group P, NF-κB and p38MAPK protein levels were down-regulated, and LcB protein level was increased (P<0. 05). Compared with group P, TNF-α and IL-6 mRNA expression was increased in group G, NF-κB and p38MAPK protein levels were increased, and LcB protein level was decreased (P<0. 05). Conclusion: The results show that pioglitazone can inhibit PAAF-stimulated THP-1 inflammation by blocking P38MAPK and NF-κB signaling pathway.
