Cineurin-regulated cascades for IL-2 gene transcription (34). Calcineurin, a Ca2+/calmodulindependent serine/threonine protein phosphatase, has been located to stimulate a nuclear transcription factor, NF-KB, by enhancing inactivation of IKB-a/MAD3, an inhibitor of NFKB (35). It has also been demonstrated that calcineurin participates in the SphK1 site induction of TNF-a gene transcription in T and B cells (36) and that consensus DNA-binding motifs for NF-KB proteins exist in the regulatory region with the TNF-a gene (37). In the light of these reports one straightforward interpretation of our findings may well be that elevated levels of intracellular cAMP by CKS-17 antagonizes calcineurin, which then suppresses NF-KB induction and results in inhibition of TNF-a gene transcription. In conclusion, the present study shows that this extremely TLR3 manufacturer conserved retroviral octadecapeptide induces remarkable levels of intracellular cAMP by means of stimulation of adenylate cyclase in a human monocyte cell line -and in human PBMC. cAMP controls physiologic cellular responses, including cell development and differentiation, also as immune effector functions (18). Of interest in this context, human immunodeficiency virus proteins have already been not too long ago shown to impair lymphocyte proliferation by induction of intracellular cAMP levels (38). Therefore, CKS-17, hugely conserved amongst several retroviral envelope elements, could impact various physiologic cellular functions, at the same time as cytokine gene expression, by increasing intracellular levels of cAMP. Our observations may perhaps as a result be relevant to understanding the molecular mechanism(s) by which retrovirus infections influence cellular functions, like immune functions.We thank Claudine Baird for assistance inside the preparation of this manuscript. This function was supported by the Eleanor Naylor Dana Charitable Trust, National Institutes of Well being Grants AG-05633 and CA41061, Ronald McDonald Charities, and the Newland Foundation.1. Peterson, R. D. A., Hendrickson, R. Fantastic, R. A. (1963) Proc. Soc. Exp. Biol. Med. 114, 517-520. 2. Snyderman, R. Cianciolo, G. J. (1984) Immunol. Today five, 240-244. 3. Great, R. A., Haraguchi, S., Lorenz, E. Day, N. K. (1991) Int. J. Immunopharmacol. 13, 1-7. four. Pahwa, S., Pahwa, R., Superior, R. A., Gallo, R. C. Saxinger, C. (1986) Proc. Natl. Acad. Sci. USA 83, 9124-9128. five. Engelman, R. W., Fulton, R. W., Fantastic, R. A. Day, N. K. (1985) Science 227, 1368-1370. 6. Yasuda, M., Excellent, R. A. Day, N. K. (1987) Clin. Exp. Immunol. 69, 240-245. 7. Mitani, M., Cianciolo, G. J., Snyderman, R., Yasuda, M., Very good, R. A. Day, N. K. (1987) Proc. Natl. Acad. Sci. USA 84,237-240. 8. Ogasawara, M., Cianciolo, G. J., Snyderman, R., Mitani, M., Very good, R. A. Day, N. K. (1988) J. Immunol. 141, 614-619. 9. Ogasawara, M., Haraguchi, S., Cianciolo, G. J., Mitani, M., Great, R. A. Day, N. K. (1990) J. Immunol. 145, 456-462. ten. Ogasawara, M., Cianciolo, G. J., Mitani, M., Kizaki, T., Superior, R. A. Day, N. K. (1991) Cancer Detect. Prev. 15, 205-209. 11. Haraguchi, S., Liu, W. T., Cianciolo, G. J., Great, R. A. Day, N. K. (1992) Cell. Immunol. 141, 388-397. 12. Haraguchi, S., Superior, R. A., Cianciolo, G. J. Day, N. K. (1992) J. Leukocyte Biol. 52, 469-472. 13. Haraguchi, S., Superior, R. A., Cianciolo, G. J., James-Yarish, M. Day, N. K. (1993) J. Immunol. 151, 2733-2741. 14. Haraguchi, S., Fantastic, R. A., James-Yarish, M., Cianciolo, G. J. Day, N. K. (1995) Proc. Natl. Acad. Sci. USA 92, 3611-3615.Immunology: Haraguchi et al15. Cianciolo, G. J., Kipnis,.