Molecular understanding of cytokine -steroid hormones dialogue: Implications for human diseases

DRUKER, J.; LIBERMAN, A. C.; ACUÑA, M.; GIACOMINI, D.; REFOJO, D.; SILBERSTEIN, S.; PAEZ PEREDA, M.; STALLA, G. K.; HOLSBOER, F.; ARZT, E.

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES.

Año: 2006

0077-8923

Highly sophisticated mechanisms confer to the immune system the capacity to respond with a certain degree of autonomy. However, the final outcome of an adaptative immune response depends on the interaction with other systems of the organism. The immune-neuroendocrine systems have an intimate cross communication making possible a satisfactory response to environmental changes. Part of this interaction occurs through cytokines and steroid hormones. The last step of this cross talk is the molecular level. Along this chapter we will focus on the physical and functional interrelationship between cytokines signaling pathway activated transcriptions factors (TFs) and steroid receptors, in different cell models were the signals triggered by cytokines and steroid hormones have major roles: (1) - The ligand dependent activated glucocorticoid receptor influence on the genetic program that specifies lineage commitment in T helper cell differentiation. How posttranslational modifications of several TFs as well as nuclear hormone receptors could be implicated in the molecular cross-talk between the immune-neuroendocrine messengers will also be discussed. (2) - Glucocorticoid antagonism on the TCR-induced T cell apoptosis. (3)- Estrogen receptor/TGFb family proteins molecular interaction implicated on pituitary prolactinomas pathogenesis. The functional cross talk at the molecular level between immune and steroids signals is essential to determinate an integrative response to both mediators (which in the last instance results in a new gene activation/repression profile) and constitutes the ultimate integrative level of interaction between the immune and neuroendocrine systems.