INTRODUCTION: Inflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis. METHODS: Our study investigated the expression of IL-1β, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson´s trichrome. RESULTS: In T1DM, HBCs showed inflammatory activation characterised by increased IL-1β and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1β and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect. CONCLUSION: The expression profiles of IL-1β, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1β expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.

• Klíčová slova
• CYP epoxygenases, gestational diabetes mellitus, hofbauer cells, placental inflammation, soluble epoxide hydrolase, type 1 diabetes mellitus,
• MeSH
• diabetes mellitus 1. typu * metabolismus   MeSH
• gestační diabetes * MeSH
• interleukin-10 metabolismus   MeSH
• lidé MeSH
• placenta metabolismus   MeSH
• těhotenství MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interleukin-10 MeSH

The gateway reflex is a mechanism by which neural inputs regulate chemokine expression at endothelial cell barriers, thereby establishing gateways for the invasion of autoreactive T cells into barrier-protected tissues. In this study, we hypothesized that rod photoreceptor dysfunction causes remodeling of retinal neural activity, which influences the blood-retinal barrier and the development of retinal inflammation. We evaluated this hypothesis using Gnat1rd17 mice, a model of night blindness with late-onset rod-cone dystrophy, and experimental autoimmune uveoretinitis (EAU). Retinal remodeling and its effect on EAU development were investigated by transcriptome profiling, target identification, and functional validation. We showed that Gnat1rd17 mice primarily underwent alterations in their retinal dopaminergic system, triggering the development of an exacerbated EAU, which was counteracted by dopamine replacement with L-DOPA administered either systemically or locally. Remarkably, dopamine acted on retinal endothelial cells to inhibit NF-κB and STAT3 activity and the expression of downstream target genes such as chemokines involved in T cell recruitment. These results suggest that rod-mediated dopamine release functions in a gateway reflex manner in the homeostatic control of immune cell entry into the retina, and the loss of retinal dopaminergic activity in conditions associated with rod dysfunction increases the susceptibility to autoimmune uveitis.

• Klíčová slova
• Gnat1, NF-κB, STAT3, blood–retinal barrier, dopamine, endothelial cells, experimental autoimmune uveoretinitis, gateway reflex, night blindness, rod-cone dystrophy,
• MeSH
• buněčné linie MeSH
• dopamin metabolismus   MeSH
• endoteliální buňky metabolismus   patologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• NF-kappa B metabolismus   MeSH
• retina metabolismus   patologie   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• uveitida metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dopamin MeSH
• NF-kappa B MeSH
• Stat3 protein, mouse MeSH Prohlížeč
• transkripční faktor STAT3 MeSH

There is growing evidence that some members of cytochrome P450 enzymes contribute to regulation of normal prenatal development. CYP epoxygenases (CYP2C and CYP2J subfamilies) convert arachidonic acid into four regioisomeric epoxyeicosatrienoic acids (EETs), biologically active molecules involved in mitogenesis and cell signaling. Almost nothing is known about localization of their expression in tissues during human prenatal development. The spatio-temporal expression pattern of CYP2C8, CYP2C9, CYP2C19 and CYP2J2 in human embryonic/fetal intestines, liver, and kidney was investigated by immunohistochemical method. CYP epoxygenases are expressed already in early stages of development in these embryonic/fetal tissues (as early as 7th week of IUD in the intestines, 5th week of IUD in the liver, and 6th week of IUD in the kidney). In kidney, CYP epoxygenases are expressed in the metanephrogenic blastema (but not in the uninduced mesenchyme) and in the tubular system. In the intestines, diverse CYP epoxygenases distribution along crypt-villus axis could suggest role in cell differentiation. Moreover, we detected higher CYP2J2 level in these organs than in adult tissue samples.

• Klíčová slova
• CYP epoxygenases, human embryos, intestine, kidney, liver,
• MeSH
• časové faktory MeSH
• cytochrom P-450 CYP2J2 MeSH
• cytochrom P450 CYP2C8 genetika   MeSH
• embryo savčí enzymologie   MeSH
• imunohistochemie MeSH
• játra embryologie   enzymologie   MeSH
• ledviny embryologie   enzymologie   MeSH
• lidé embryologie   MeSH
• střeva embryologie   enzymologie   MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• vývojová regulace genové exprese * MeSH
• Check Tag
• lidé embryologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CYP2J2 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP2J2 MeSH
• cytochrom P450 CYP2C8 MeSH
• systém (enzymů) cytochromů P-450 MeSH