Prostaglandin generation in vitro by peripheral blood mononuclear cells in co-culture with human thyroid cells.

Previous studies from this laboratory have indicated that peripheral blood mononuclear cells co-cultured with human thyroid cells produce soluble factors that can subsequently stimulate cyclic adenosine 3’,5’-monophosphate (cyclic AMP) generation in fresh thyroid cells. Earlier data obtained by bioassay suggested that these factors are prostaglandins. In the present study, concentrations of prostaglandins were measured directly by radioimmunoassay. Prostaglandin E (PGE), prostaglandin B (PGB), and prostaglandin F (PGF) were initially undetectable in the culture medium, but then increased progressively over 7 days. Maximal PGE concentrations attained (mean of 4 X 10m8 M) were intermediate to PGF and PGB concentrations, with the latter being the lowest. Examination of the dose-response relationship between a variety of prostaglandins and thyroid cell cyclic AMP stimulation suggested that only PGE was generated in the cell co-cultures at a concentration sufficient to stimulate thyroid cell cyclic AMP content. Thin layer chromatography of radiolabeled prostaglandins generated from [%larachidonic acid confirmed that significant quantities of PGES were produced by thyroid cell-leukocyte co-cultures. Thyroid cells cultured alone released no detectable prostaglandins into the culture medium. Peripheral blood mononuclear cells cultured alone released prostaglandins into the medium, but at considerably lower concentrations than when these cells were incubated together with thyroid cells. Indomethacin present in the medium during cell co-cultures inhibited prostaglandin generation with a half-maximal inhibitory concentration of approximately lOWe M. The presence of cortisol similarly inhibited prostaglandin generation with a half-maximal inhibitory concentration of 5 x 10-’ M. These concentrations of indomethacin and cortisol are the same as those necessary to inhibit halfmaximally the accumulation of bioactivity in the medium. Evidence is presented to suggest that actual contact between thyroid cells and peripheral blood mononuclear cells is important in the enhancement of prostaglandin generation by the latter cells.