Characterization of secretory type IIA phospholipase A2 (sPLA2-IIA) as a glycyrrhizin (GL)-binding protein and the GL-Induced inhibition of the CK-II-mediated stimulation of sPLA2-IIA activity in vitro

By means of heparin-affinity and glycyrrhizin (GL)-affinity column chromatographies (HPLC), a GL-binding phospholipase A(2) (gbPLA(2)) was selectively purified from the synovial fluids of patients with rheumatoid arthritis. This purified gbPLA(2) was identified as a secretory type ITA PLA, (sPLA(2)-IIA) since it was crossreacted with anti-sPLA(2)-IIA serum. The activity of purified sPLA(2)IIA was inhibited by glycyrrhetinic acid (GA) and a GA derivative (oGA) in a dose-dependent manner, but it was more sensitive to GA than GL. Furthermore, it was found that (i) purified sPLA(2)-IIA is phosphorylated by casein kinase II (CK-II) in vitro; (ii) this phosphorylation induces in a significant stimulation of PLA(2) activity; and (iii) oGA at one-tenth the concentration of GL inhibits the CK-II-mediated stimulation of sPLA(2)-IIA activity. These results show that (i) sPLA(2)-IIA is a GL-binding protein; and (ii) CK-II mediates stimulation of its PLA, activity in vitro.