Integrative study of hypothalamus-pituitary-thyroid-immune system interaction: thyroid hormone-mediated modulation of lymphocyte activity through the protein kinase C signaling pathway.

KLECHA, AJ; GENARO, AM; GORELIK, G; BARREIRO ARCOS, ML; MAGALI SILBERMAN, D; SCHUMAN, MARIANO LUIS; GARCIA , SILVIA INES; PIROLA, CARLOS JOSE; CREMASCHI, GA

Journal of Endocrinology

Año: 2006 vol. 189 p. 45 - 55

0022-0795

Thyroid hormones play critical roles in differentiation, growth and metabolism, but their participation in immune system regulation have not been completely elucidated. Modulating in vivo thyroid status, an integrative analysis of the hypothalamus-pituitary-thyroid (HPT) axis on T and B lymphocyte activity was performed. The participation of protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyper- and hypothyroid mice displayed higher and lower T- and B-mitogen induced proliferation respectively than euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher and lower in T and B cells from hyper- and hypothyroid mice respectively compared to controls. Levels of thyroid stimulating (TSH) and TSH-releasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBC) and restimulation in vitro spleen cells from hyper- or hypothyroid mice showed increased or decreased production of IL-2 and IFN-ãin vivo thyroid status, an integrative analysis of the hypothalamus-pituitary-thyroid (HPT) axis on T and B lymphocyte activity was performed. The participation of protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyper- and hypothyroid mice displayed higher and lower T- and B-mitogen induced proliferation respectively than euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher and lower in T and B cells from hyper- and hypothyroid mice respectively compared to controls. Levels of thyroid stimulating (TSH) and TSH-releasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBC) and restimulation in vitro spleen cells from hyper- or hypothyroid mice showed increased or decreased production of IL-2 and IFN-ãthyroid status, an integrative analysis of the hypothalamus-pituitary-thyroid (HPT) axis on T and B lymphocyte activity was performed. The participation of protein kinase C (PKC) signaling pathway and the release of some cytokines upon antigenic stimulation were analyzed. Lymphocytes from hyper- and hypothyroid mice displayed higher and lower T- and B-mitogen induced proliferation respectively than euthyroid animals. Reversion of hypothyroid state by triiodothyronine (T3) administration recovered proliferative responses. No differences were found in lymphoid subset balance. Both total PKC content and mitogen-induced PKC translocation were higher and lower in T and B cells from hyper- and hypothyroid mice respectively compared to controls. Levels of thyroid stimulating (TSH) and TSH-releasing (TRH) hormones were not directly related to lymphocyte proliferative responses. After immunization with sheep red blood cells (SRBC) and restimulation in vitro spleen cells from hyper- or hypothyroid mice showed increased or decreased production of IL-2 and IFN-ãin vitro spleen cells from hyper- or hypothyroid mice showed increased or decreased production of IL-2 and IFN-ãã cytokines, respectively. Additionally an increase in IL-6 and IFN-ã levels was found in hyperthyroid cells after in vivo injection and in vitro restimulation with lipopolysaccharide (LPS). Our results show for the first time a thyroid hormone mediated-regulation of PKC content and of cytokine production in lymphocytes, that could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. They also point out the important role that these hormones play in regulating lymphocyte reactivity.ã levels was found in hyperthyroid cells after in vivo injection and in vitro restimulation with lipopolysaccharide (LPS). Our results show for the first time a thyroid hormone mediated-regulation of PKC content and of cytokine production in lymphocytes, that could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. They also point out the important role that these hormones play in regulating lymphocyte reactivity.in vivo injection and in vitro restimulation with lipopolysaccharide (LPS). Our results show for the first time a thyroid hormone mediated-regulation of PKC content and of cytokine production in lymphocytes, that could be involved in the altered responsiveness to mitogen-induced proliferation of T and B cells. They also point out the important role that these hormones play in regulating lymphocyte reactivity.