دورية أكاديمية
Immunomodulatory effects of progesterone and selective ligands of membrane progesterone receptors.
| العنوان: | Immunomodulatory effects of progesterone and selective ligands of membrane progesterone receptors. |
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| المؤلفون: | Polikarpova AV; Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia., Levina IS; Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia., Sigai NV; Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia., Zavarzin IV; Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow 119991, Russia., Morozov IA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia., Rubtsov PM; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia., Guseva AA; Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia., Smirnova OV; Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia., Shchelkunova TA; Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia. Electronic address: schelkunova-t@mail.ru. |
| المصدر: | Steroids [Steroids] 2019 May; Vol. 145, pp. 5-18. Date of Electronic Publication: 2019 Feb 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0404536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5867 (Electronic) Linking ISSN: 0039128X NLM ISO Abbreviation: Steroids Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Elsevier Original Publication: San Francisco. |
| مواضيع طبية MeSH: | Cell Membrane/*metabolism , Immunologic Factors/*pharmacology , Progesterone/*pharmacology , Receptors, Progesterone/*metabolism, Female ; Gene Expression Regulation/drug effects ; Humans ; Interleukin-10/genetics ; Interleukin-10/metabolism ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Jurkat Cells ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Ligands ; Male ; RNA, Messenger/genetics ; Sex Characteristics ; Toll-Like Receptor 4/genetics ; Tumor Necrosis Factor-alpha/genetics ; Tumor Necrosis Factor-alpha/metabolism |
| مستخلص: | Progesterone (P4) and its analogues regulate various reproductive processes, such as ovulation, implantation, pregnancy maintenance and delivery. In these processes, an important role is played by the immune cells recruited to the female reproductive organs and tissues, where they are exposed to the action of P4. Progestins regulate cellular processes, acting through nuclear steroid receptors (nSRs), membrane P4 receptors (mPRs), and through the sensors. It remains unclear, what type of receptors is used by P4 and its derivatives to exert their effect on the immune cells and how similar their effects are in different types of these cells. We have previously synthesized new progesterone derivatives, among which two selective mPRs ligands, not interacting with nSRs were identified. The objective of this study was to examine the effects of P4 and new selective mPRs ligands on the expression of pro- and anti-inflammatory cytokines in activated human peripheral blood mononuclear cells (PBMCs), THP-1 monocyte cells, and Jurkat T cells. It was demonstrated that the action of P4 and selective ligands was unidirectional, but in different types of the immune cells, their effects were different, and sometimes even opposite. In PBMCs, exposure to these steroids resulted in the increase of mRNA and secreted protein levels of IL-1β, TNFα, and IL-6 cytokines, as well as in the increase of INFγ mRNA level, decrease of IL-2 mRNA level, increase of TGFβ mRNA level, and decrease of IL-4 mRNA and IL-10 secreted protein levels. In monocytes, similarly to PBMCs, expression of IL-1β and TNFα mRNA was increased, but expression of IL-10 was also increased, and the TGFβ expression statistically significantly remained the same. In Jurkat T cells, expression of IL-2 and TNFα mRNA decreased, while expression of IL-10 increased, and expression of TGFβ did not change. Thus, progestins act on the immune cells through mPRs and have both pro- and anti-inflammatory effects, depending on the phenotypes of these cells. The data obtained are important for understanding the complexity of the immune system regulation by progestins, which depends on the type of the immune cells and individual characteristics of the immune system. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Gene expression; Immune cells; Inflammation; Progesterone; Receptors; Selective ligands |
| المشرفين على المادة: | 0 (Immunologic Factors) 0 (Interleukin-1beta) 0 (Interleukin-6) 0 (Ligands) 0 (RNA, Messenger) 0 (Receptors, Progesterone) 0 (Toll-Like Receptor 4) 0 (Tumor Necrosis Factor-alpha) 130068-27-8 (Interleukin-10) 4G7DS2Q64Y (Progesterone) |
| تواريخ الأحداث: | Date Created: 20190213 Date Completed: 20200221 Latest Revision: 20200221 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.steroids.2019.02.009 |
| PMID: | 30753845 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-5867 |
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| DOI: | 10.1016/j.steroids.2019.02.009 |