Studies on the mechanism of caffeine action in alveolar macrophages: caffeine elevates cyclic adenosine monophosphate level and prostaglandin synthesis.

We have previously reported that the effects of caffeine on alveolar macrophages are dose-dependent; thus, at low concentrations caffeine prevents apoptosis and at moderate concentrations, the cells proceed into apoptosis. In the current study, the mechanism of caffeine action via prostaglandin synthesis and cyclic adenosine monophosphate (cAMP) was investigated using moderate concentrations of caffeine. The results show that the combination of caffeine with indomethacin, an inhibitor of prostaglandin synthesis, mediated caffeine's effect by increasing cellular viability and lowering superoxide anion production and DNA fragmentation. However, addition of exogenous prostaglandin E2 (PGE2) to the culture in the presence of caffeine had the opposite effect, in which the viability was decreased and anion superoxide production was increased. Incubation of macrophages with exogenous dibutyryl cAMP showed nearly similar effects to caffeine. At low concentrations (<50 micromol/L), higher viability and lower superoxide production pattern were evident and at higher concentrations (>50 micromol/L) the cells proceeded into apoptosis. Therefore, it is suggested that caffeine exerts its effects on macrophages by altering cAMP level and prostaglandin synthesis.