The pituitary hormone prolactin (PRL) has been shown to have stimulatory effects on immune processes in a number of in vivo and in vitro model systems. The molecular mechanisms of these effects are unknown. Recently, Russell and coworkers, and others, have described mutually antagonistic interactions between PRL and the potent immunosuppressant cyclosporin A (CSA) in several immunologic assays. The molecular mechanisms of these interactions are also unknown. However, the existence -of distinct functional interactions between PRL and CSA provides a unique opportunity to examine in detail the molecular mechanisms of these interactions, and advance our knowledge of neuroendocrine-immune system relationships in general. In addition to basic immunological interest, the interaction between PRL and CSA also suggests new therapeutic approaches to immunosuppression based on modulation of PRL. In order to understand the molecular basis of PRL - CSA interactions and their importance in immunity, three specific aims are outlined in this proposal:
Aim 1. Examination of the mechanism of molecular interactions between PRL and CSA;
Aim 2. Identification and initial biochemical characterization of the lymphoid PRL receptor;
and Aim 3. Examination of direct effects of PRL on the expression of selected immunoregulatory molecules. These goals will be met utilizing radioligand binding assays, and biochemical and immunochemical techniques of cell-surface molecule isolation and analysis. The results of these-studies will serve as the basis for future study of the molecular biology of PRL actions in the immune system.
| Koh, C Y; Phillips, J T (1993) Prolactin receptor expression by lymphoid tissues in normal and immunized rats. Mol Cell Endocrinol 92:R21-5 |
| Girolomoni, G; Phillips, J T; Bergstresser, P R (1993) Prolactin stimulates proliferation of cultured human keratinocytes. J Invest Dermatol 101:275-9 |
| Phillips, J T; Meyers, K A (1992) Adoptive transfer of experimental allergic encephalomyelitis using serum-free, chemically defined in vitro culture conditions. J Neuroimmunol 40:111-4 |
