Aspirin and vitamin E synergistically inhibit the induction of cyclooxygenase-2 in mouse macrophages

The inducible form of cyclooxygenase, COX-2, is considered a key enzyme in inflammatory processes. The present study investigates whether the antiinflammatory agent aspirin in combination with d-α-tocopherol acetate (vitamin E) inhibits the lipopolysaccharide (LPS)-induced (a) accumulation of prostaglandin (PG) E₂(b) expression of COX-2 protein (c) expression of COX-2 mRNA in mouse macrophages (J774.1A). The accumulation of PGE₂ (measured by radioimmunoassay)due to LPS (1 microM) was significantly attenuated by the cyclooxygenase inhibitor aspirin (1-100 microM)or vitamin E (100-500 microM). The treatment of LPS-primed cells with 1 or 3 microM aspirin resulted in 18% and 53% inhibition of PGE₂ accumulation, respectively. In the presence of vitamin E (300 microM), inhibition of PGE₂ accumulation was markedly enhanced (54% at 1 microM and 65% at 3 microM). Moreover the expression of COX-2 protein and mRNA (measured by Western and Northern blot analysis, respectively) was virtually abolished by the combined treatment of aspirin and vitamin E, whereas the two agents alone were only modestly effective. In conclusion, the inhibitory effect of aspirin on LPS-induced COX-2 expression and PGE₂ formation in J774.1A cells is augmented in an overadditive fashion by vitamin E. Thus, antiinflammatory therapy might be successful with low dose aspirin when combined with vitamin E thereby possibly avoiding the side effects of the usually required high dose aspirin treatment.