The Production Mechanism of TNF-α and IL-6 by Group IIA Phospholipase A₂

Abstract

Background: Secretory phospholipase A 2 (sPLA 2 ) are a group of extracellular enzymes that release fatty acids at the sn-2 position of phospholipids. Group IIA sPLA 2 (sPLA 2 -IIA) has been detected in the inflammatory fluids, and its plasma level increases in the inflammatory disease. This study examined the effect of sPLA 2-IIA on mouse macropahges in order to investigate the potential mechanism of sPLA 2 -induced inflammation.Materials and Methods: Wild type PLA 2 and mutant H48Q PLA 2 were purified from HEK293 cells transfected with the corresponding plasmids, and the PLA 2 activities were measured using 1-palmitoyl-2-[1-14 C]linoleoyl-3-phosphatidylethanolamine as substrates. The TNF-α and IL-6 released in the supernatants were determined by ELISA. In addition, the TNF-α and IL-6 mRNA were analyzed by RT-PCR.Results: sPLA 2 -IIA stimulated the production of TNF-α and IL-6 in a dose-and time-dependent manner. In addition, the effect of sPLA 2 -IIA on cytokine production from the macrophage was found to be associated with the accumulation of their specific mRNA. The mRNA levels of TNF-α and IL-6 peaked at 2 and 6 hours in a time-dependent manner, respectively. the binding of sPLA 2 -IIA to the receptors.