Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice
| Autor: | Bishnu Devi Maharjan, Kimie Nakagawa, Hiroshi Hasegawa, Morichika Konishi, Yukihiko Sugimoto, Nurhanani Razali, Tomoaki Inazumi, Hirofumi Hohjoh |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Pharmaceutical Science Thymus Gland Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound Thromboxane A2 Th2 Cells 0302 clinical medicine Internal medicine medicine Animals Involution (medicine) Caloric Restriction Pharmacology Mice Inbred ICR Thymic involution Aspirin Anti-Inflammatory Agents Non-Steroidal Prostanoid Organ Size General Medicine Th1 Cells Diet Thromboxane B2 030104 developmental biology Endocrinology chemistry 030220 oncology & carcinogenesis Ionomycin Prostaglandins Cytokines Etodolac Prostaglandin D2 |
| Zdroj: | Biological and Pharmaceutical Bulletin. 43:649-662 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b19-00838 |
| Popis: | Multiple external and internal factors have been reported to induce thymic involution. Involution involves dramatic reduction in size and function of the thymus, leading to various immunodeficiency-related disorders. Therefore, clarifying and manipulating molecular mechanisms governing thymic involution are clinically important, although only a few studies have dealt with this issue. In the present study, we investigated the molecular mechanisms underlying thymic involution using a murine acute diet-restriction model. Gene expression analyses indicated that the expression of T helper 1 (Th1)-producing cytokines, namely interferon-γ and interleukin (IL)-2, was down-regulated, while that of Th2-producing IL-5, IL-6, IL-10 and IL-13 was up-regulated, suggesting that acute diet-restriction regulates the polarization of naive T cells to a Th2-like phenotype during thymic involution. mRNAs for prostanoid biosynthetic enzymes were up-regulated by acute diet-restriction. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses detected the increased production of prostanoids, particularly prostaglandin D2 and thromboxane B2, a metabolite of thromboxane A2, in the diet-restricted thymus. Administration of non-steroidal anti-inflammatory drugs, namely aspirin and etodolac, to inhibit prostanoid synthesis suppressed the biased expression of Th1- and Th2-cytokines as well as molecular markers of Th1 and Th2 cells in the diet-restricted thymus, without affecting the reduction of thymus size. In vitro stimulation of thymocytes with phorbol myristate acetate (PMA)/ionomycin confirmed the polarization of thymocytes from diet-restricted mice toward Th2 cells. These results indicated that the induced production of prostanoids during diet-restriction-induced thymic involution is involved in the polarization of naive T cells in the thymus. |
| Databáze: | OpenAIRE |
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