engleski

Prenatal ethanol exposure's influence on lymphopoietic transcription factors

Transcription factors, such as Ikaros and Notch families play a crucial role in lymphocyte development. Thus, loss or mutation of the Ikaros gene leads to a decreasing number of lymphocytes, while Aiolos mutant mice suffer remarkable changes in their B cell subpopulations. Ikaros is also important in promotion of early-born neuronal fates in the cerebral cortex. Further Ikaros family members, Eos, Helios and Pegasus are involved in lymphocyte development, and same factors play important role in neural and brain development. Besides Ikaros family, Notch signalling is important part of directing the hematopoietic cell fate and loss of function experiments showed its main role in T lymphocyte development. Its presence and expression in cells of adult nervous system implies its heterogenic developmental role. Understanding of the development of immune system in rodents is mostly due to experiments in mice. Rats represent a common experimental model, very useful because of their genetic diversity, and the research results of their phenotypic and genotypic characteristics enable accelerated development of new diagnostic approaches, prevention and treatment of various diseases in humans. Since the rat represents an animal model commonly used in a broad range of pathophysiological and pharmacological studies, including those related to crosstalk between immune and other systems, the first aim of the present study was to investigate if and which of the members of Ikaros transcription factors are expressed in thymic rat lymphocytes. As an experimental system we use exposing animals to alcohol prenatally under controlled conditions. Due to the fact that factors from the Ikaros family are essential in lymphopoiesis, and that in utero exposure to ethanol affects the immune system development, we examined the impact of prenatal alcohol exposure on the expression of these factors in the adult rat thymus. In this study we confirm for the first time the expression of all known Ikaros family transcription factors in rat thymic lymphocytes. We showed that prenatal alcohol exposure induced also persistent and long lasting changes in the rat thymus. It seems that ethanol during gestation affects bone marrow cells, either the thymocyte committed precursors or the primitive selfrenewing hematopoietic stem cells.

Ethanol; Ikaros family of transcription factors

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