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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Authors: | Watanabe, Sumiko Yssel, Hans Harada, Yoshio Arai, Ken-ichi |
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Affiliation: | Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo Tokyo 108, Japan 1 Department of Human Immunology, DNAX Research Institute of Molecular and Cellular Biology Palo Alto, CA, USA |
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Abstract: | The effects of prostaglandin E2 (PGE2) on cytokine productionand proliferation of the CD4+ human helper T cell clone SP-B21were investigated. In cells stimulated with antl-CD3 mAb, PGE2inhibited cell proliferation and the production of all the cytokinesexamined. Addition of rlL-2 fully restored the prollferatlveresponse and partially restored the production of IL-4 and IL-5,but not that of other cytokines. In contrast, In cells stimulatedwith phorbol myrlstate acetate (PMA)/A23187, PGE2 enhanced theproduction of IL-4 and IL-5, and only partially inhibited theproduction of other cytokines. Therefore, the effects of PGE2vary depending on the mode of T cell activation, and the IL-4and IL-5 are regulated differently from other cytokines. Ina mobility shift assay, only the NF- B (p50/p5O) homodlmer wasobserved in a complex formed with the B sequence in unstlmulatedSP-B21 cells. When cells were stimulated with antl-CD3 mAb orPMA/A23187, a complex formation of NF- B (p50/p65) heterodlmerwith the B sequence was induced. Interestingly, PGE2 or di-butyryl(Bt2cAMP abolished the binding of NF- B (p50/p65) heterodlmerto the B sequence in cells stimulated with antl-CD3 mAb butnot with PMA/A23187. Our results suggest that the target ofPGE2 action is a component in the signal transductlon pathwayleading to the activation of protein klnase C. However, theinhibition of the T cell activation signals by PGE2 is selective.PGE2 enhanced the complex formation with NF-AT, AP-1 and CLEOsequences when the cells were activated by either anti-CD3 mAbor PMA/A23187 stimulation. It seems therefore that PGE2, byelevating cAMP levels, interferes with the activation pathwayfor NF- B but not for NF-AT, AP-1 or CLEO binding protein. |
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Keywords: | cAMP cytokines human Th0 clone prostaglandin E2 |
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