Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production

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Abstract
The effects of prostaglandin E2 (PGE2) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated. In cells stimulated with antl-CD3 mAb, PGE2 inhibited cell proliferation and the production of all the cytokines examined. Addition of rlL-2 fully restored the prollferatlve response and partially restored the production of IL-4 and IL-5, but not that of other cytokines. In contrast, In cells stimulated with phorbol myrlstate acetate (PMA)/A23187, PGE2 enhanced the production of IL-4 and IL-5, and only partially inhibited the production of other cytokines. Therefore, the effects of PGE2 vary depending on the mode of T cell activation, and the IL-4 and IL-5 are regulated differently from other cytokines. In a mobility shift assay, only the NF-χB (p50/p5O) homodlmer was observed in a complex formed with the χB sequence in unstlmulated SP-B21 cells. When cells were stimulated with antl-CD3 mAb or PMA/A23187, a complex formation of NF-χB (p50/p65) heterodlmer with the χB sequence was induced. Interestingly, PGE2 or di-butyryl (Bt2cAMP abolished the binding of NF-χB (p50/p65) heterodlmer to the χB sequence in cells stimulated with antl-CD3 mAb but not with PMA/A23187. Our results suggest that the target of PGE2 action is a component in the signal transductlon pathway leading to the activation of protein klnase C. However, the inhibition of the T cell activation signals by PGE2 is selective. PGE2 enhanced the complex formation with NF-AT, AP-1 and CLEO sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation. It seems therefore that PGE2, by elevating cAMP levels, interferes with the activation pathway for NF-χB but not for NF-AT, AP-1 or CLEO binding protein.

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