THU0053 Inhibition of arachidonic acid release from human peripheral mononuclear cells by heat shock treatment and geldanamycin

Abstract

Background Arachidonic acid and its derivatives play an important role in inflammation including arthritis. Objectives To investigate the effects of heat shock (HS) treatment and geldanamycin (GM) on the release of arachidonic acid (AA) from human peripheral blood human mononuclear cells (PBMCs) (monocytes and lymphocytes). Methods Mononuclear cells prepared from blood of healthy subjects were preincubated with 3H-AA. The release of 3H-AA incorporated into the membrane was studied after pretreatment of cells by HS (43°C, 1 h), GM and prednisolone sodium succinate (PRED). The activation of AA producing enzymes took place by the addition of phorbol 12-myristate 13-acetate (PMA) or by the combination of PMA and calcium ionophore A 23187. Results The release of AA by mononuclear cells was dose dependently inhibited by GM similarly to PRED. The treatment of cells by HS also inhibited the release of AA. An additivity was found in the inhibitions induced by GM, PRED and HS. Conclusion HS treatment can decrease the release of AA from human mononuclear cells. GM also results in a dose dependent inhibition of AA release. In the mechanism of additivity In the mechanism of additivity found when HS and GM were applied concurrently, the increased blocking of mitogen-activated kinase cascade could be involved. In the additivity induced by HS + PRED and GM + PRED combinations different pathways, the MAPK (HS, GM) and some transcription factors (PRED) simultaneously could play a role. The inhibitory effect of GM on the AA release from mononuclear cells can be a new element in its antiinflammatory actions.