Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice

• Razali Nurhanani

  Laboratory of Hygienic Sciences, Kobe Pharmaceutical University

• Hohjoh Hirofumi

  Laboratory of Hygienic Sciences, Kobe Pharmaceutical University

• Inazumi Tomoaki

  Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University

• Maharjan Bishnu Devi

  Laboratory of Hygienic Sciences, Kobe Pharmaceutical University

• Nakagawa Kimie

  Laboratory of Hygienic Sciences, Kobe Pharmaceutical University

• Konishi Morichika

  Laboratory of Microbial Chemistry, Kobe Pharmaceutical University

• Sugimoto Yukihiko

  Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University

• Hasegawa Hiroshi

  Laboratory of Hygienic Sciences, Kobe Pharmaceutical University

Abstract

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 naïve 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 naïve T cells in the thymus.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 43 (4), 649-662, 2020-04-01

  The Pharmaceutical Society of Japan

Keywords

• thymic involution
• diet-restriction
• prostanoid
• helper T cell
• inflammatory cytokine
• polarization

Details

• CRID: 1390565134844632832
• NII Article ID: 130007825267
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b19-00838
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 030335003
• PubMed: 32238706
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I030335003
• Web Site: https://www.jstage.jst.go.jp/article/bpb/43/4/43_b19-00838/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2021023026
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed