Tenidap sodium inhibits secretory non-pancreatic phospholipase A(2) synthesis by foetal rat calvarial osteoblasts.
Tenidap (TD) was initially defined as a dual inhibitor of cyclooxygenase and lipoxygenase. This study was designed to assess its inhibitory activity against proinflammatory phospholipase A(2). This study shows that TD inhibits the synthesis of pro-inflammatory secretory non-pancreatic phospholipase A(2) (sPLA(2)). Concentrations as low as 0.25 mug/ml (0.725 muM) reduced the release of sPLA(2) by 40% from foetal rat calvarial osteoblasts stimulated with IL-1beta and TNFalpha, whereas a concentration of 2.5 mug/ml (7.25 muM) reduced the release by over 80%. TD also markedly reduced the release of sPLA(2) from unstimulated cells. There was no direct inhibition of sPLA(2) enzymatic activity by TD in vitro. Northern blot analysis showed that TD did not affect the sPLA(2) mRNA levels; however, immunoblotting showed a dose-dependent reduction in sPLA(2) enzyme. These results, together with a marked reduction in sPLA(2) enzymatic activity, suggest that TD inhibits sPLA(2) synthesis at the post-transcriptional level. Therefore TD seems to inhibit the arachidonic acid cascade proximally to cyclooxygenase and lipoxygenase and its anti-inflammatory activity may be related at least in part to the inhibition of sPLA(2) synthesis.
Pruzanski
W
W
lnflammation Research Group Division of Immunology, Wellesley Hospital University of Toronto Ontario Toronto M4Y 1J3 Canada.
Kennedy
B P
BP
Bosch
H
H
Stefanski
E
E
Wloch
M
M
Vadas
P
P