Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes

Abstract

Calcium (Ca 2+ ) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca 2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca 2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca 2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca 2+ permeable ion channels in the plasma membrane open. The Ca 2+ release-activated (CRAC) channel is the most prominent Ca 2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca 2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca 2+ channels in the plasma membrane are the voltage-gated Ca 2+ (Ca V ) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca 2+ channels was detected in the PBMCs where the Ca V 2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca V 2.1 and Ca V 3.2 genes were up-regulated only in pregnancy and the Ca V 1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.