0000000000348978
AUTHOR
Elke Butt
Activation of cGMP-dependent Protein Kinase Iβ Inhibits Interleukin 2 Release and Proliferation of T Cell Receptor-stimulated Human Peripheral T Cells
Several major functions of type I cGMP-dependent protein kinase (cGK I) have been established in smooth muscle cells, platelets, endothelial cells, and cardiac myocytes. Here we demonstrate that cGK Ibeta is endogenously expressed in freshly purified human peripheral blood T lymphocytes and inhibits their proliferation and interleukin 2 release. Incubation of human T cells with the NO donor, sodium nitroprusside, or the membrane-permeant cGMP analogs PET-cGMP and 8-pCPT-cGMP, activated cGK I and produced (i) a distinct pattern of phosphorylation of vasodilator-stimulated phosphoprotein, (ii) stimulation of the mitogen-activated protein kinases ERK1/2 and p38 kinase, and, upon anti-CD3 stimu…
Health-Relevant Phenotypes in the Offspring of Mice Given CAR Activators Prior to Pregnancy
Hepatic induction in response to drugs and environmental chemicals affects drug therapies and energy metabolism. We investigated whether the induction is transmitted to the offspring. We injected 3-day- and 6-week-old F0 female mice with TCPOBOP, an activator of the nuclear receptor constitutive androstane receptor (CAR, NR1I3), and mated them 1-6 weeks afterward. We detected in the offspring long-lasting alterations of CAR-mediated drug disposition, energy metabolism, and lipid profile. The transmission to the first filial generation (F1) was mediated by TCPOBOP transfer from the F0 adipose tissue via milk, as revealed by embryo transfer, crossfostering experiments, and liquid chromatograp…