The Production Mechanism of TNF-alpha and IL-6 by Group IIA Phospholipase A2.
10.12701/yujm.2004.21.2.177
- Author:
Jae Hong AHN
1
;
Dae Won PARK
;
Jin Hee KIM
;
Jei Jun BAE
;
Yeun Kyoung BAE
;
Yoon Ki PARK
Author Information
1. Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University, Daegu, Korea. yoonki@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Group IIA phospholipase A2;
TNF-alpha;
IL-6;
Macrophage cells;
Inflammation
- MeSH:
Animals;
Enzyme-Linked Immunosorbent Assay;
Fatty Acids;
Group II Phospholipases A2*;
HEK293 Cells;
Inflammation;
Interleukin-6*;
Macrophages;
Mice;
Phospholipases A2, Secretory;
Phospholipids;
Plasma;
Plasmids;
RNA, Messenger;
Tumor Necrosis Factor-alpha*
- From:Yeungnam University Journal of Medicine
2004;21(2):177-190
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Secretory phospholipase A2 (sPLA2) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA2 (sPLA2-IIA) has been detected in the inflammatory fluids, and its plasma level increases in the inflammatory disease. This study examined the effect of sPLA2-IIA on mouse macropahges in order to investigate the potential mechanism of sPLA2-induced inflammation. MATERIALS AND METHODS: Wild type PLA2 and mutant H48Q PLA2 were purified from HEK293 cells transfected with the corresponding plasmids, and the PLA2 activities were measured using 1-palmitoyl-2-[1- (14) C]linoleoyl-3-phosphatidylethanolamine as substrates. The TNF-alpha and IL-6 released in the supernatants were determined by ELISA. In addition, the TNF-alpha and IL-6 mRNA were analyzed by RT-PCR. RESULTS: sPLA2-IIA stimulated the production of TNF-alpha and IL-6 in a dose- and time-dependent manner. In addition, the effect of sPLA2-IIA on cytokine production from the macrophage was found to be associated with the accumulation of their specific mRNA. The mRNA levels of TNF-alpha and IL-6 peaked at 2 and 6 hours in a time-dependent manner, respectively. CONCLUSION: In conclusion, the production of proinflammatory cytokine might be mediated by the binding of sPLA2-IIA to the receptors.