engleski

Understanding the mechanisms of biomodulation with transcriptomics toys

The word "biomodulation" has been traditionally used in immunology for procedures that manipulate body's immune system. In its broadest meaning, this word can be used for any process that influences biological processes. Proteins are effector molecules of these actions, but our present inability to detect specific proteins (lack of monoclonal antibodies) or a small amount of them (sensitivity of proteomic methods) moves our focus to transcriptomics. Biomodulation at the level of the transcriptome can be explained through the action of vitamin D. Growing evidence indicates that 1 , 25(OH)2D3 is an important modulator of the immune responses, consistent with broad expression of the vitamin D receptor (VDR) in cells of the immune system and the capacity of 1 , 25(OH)2D3 to regulate cellular differentiation. Mice in which the VDR gene had been ablated displayed abnormal pro-inflammatory T helper 1 (Th1) cell development and mice rendered 1 , 25(OH)2D3 deficient by knockout of the gene encoding 25-hydroxyvitamin D3 1 -hydroxylase were deficient in peripheral T lymphocytes. Moreover, 1, 25(OH)2D3 inhibits dendritic cell maturation, which is critical for T cell-mediated immune responses, and reduces expression of the cytokine interleukin-12 (IL-12), whose signaling is critical for Th1 maturation. Microarray analyses have revealed some of the molecular events that are connected with other biomodulatory action of 1 , 25(OH)2D3/its analogue EB1089 - a chemoprevention ; it is antiproliferative, it induces cellular differentiation, and it has potential genoprotective effects. All these results can be obtained in only one carefully designed microarray experiment and, ideally, should be checked at the level of proteins. Hence, microarray profiling is a very powerful method, but results obtained by microarray should be applied with the greatest care and should not be interpreted as final without confirmation at the protein level, whenever it is possible.

vitamin D; dendritična stanica; biomodulacija; DNA-čip

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