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J Yeungnam Med Sci > Volume 21(2); 2004 > Article
Yeungnam University Journal of Medicine 2004;21(2):177-190.
DOI:    Published online December 31, 2004.
The Production Mechanism of TNF-alpha and IL-6 by Group IIA Phospholipase A2.
Jae Hong Ahn, Dae Won Park, Jin Hee Kim, Jei Jun Bae, Yeun Kyoung Bae, Yoon Ki Park
1Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University, Daegu, Korea.
2Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea.
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.
Key Words: Group IIA phospholipase A2, TNF-alpha, IL-6, Macrophage cells, Inflammation
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