Molecular understanding of cytokine-steroid hormone dialogue: implications for human diseases.
Highly sophisticated mechanisms confer upon 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 crosstalk is at the molecular level. In this article we will focus on the physical and functional interrelationship between cytokine signaling pathway-activated transcription factors (TFs) and steroid receptors in different cell models, where the signals triggered by cytokines and steroid hormones have major roles: (1) the ligand-dependent-activated glucocorticoid receptor (GR) influence the genetic program that specifies lineage commitment in T helper (Th) cell differentiation. How posttranslational modifications of several TFs as well as nuclear hormone receptors could be implicated in the molecular crosstalk between the immune-neuroendocrine messengers is discussed. (2) glucocorticoid (GC) antagonism on the TCR-induced T cell apoptosis. (3) estrogen receptor/TGF-beta family proteins molecular interaction implicated on pituitary prolactinomas pathogenesis. The functional crosstalk at the molecular level between immune and steroids signals is essential to determine 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.
Druker
Jimena
J
Laboratorio de Fisiología y Biología Molecular, Departmento de Fisiologiía y Biooogía Molecular y Celular, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.
Liberman
Ana C
AC
Acuña
Matías
M
Giacomini
Damiana
D
Refojo
Damián
D
Silberstein
Susana
S
Pereda
Marcelo Paez
MP
Stalla
Günter K
GK
Holsboer
Florian
F
Arzt
Eduardo
E
D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015213:Neuroimmunomodulation / Q000276:immunology*; D009490:Neurosecretory Systems / Q000276:immunology* / Q000378:metabolism; D013256:Steroids / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D013256:Steroids