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

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 D 2 and thromboxane B 2 , a metabolite of thromboxane A 2 , 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 Th1and 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.

Influence of Inhibition of COX-2-Dependent Lipid Metabolism on Regulation of UVB-Induced Keratinocytes Apoptosis by Cannabinoids

“…Moreover, EP1 agonists in vitro promote Th1 responses [ 45 ], while PGE2 in vivo induces Th17 cell differentiation, as well as the production of pro-inflammatory cytokines [ 46 ]. On the other hand, inhibition of COX-2 by non-steroidal anti-inflammatory drugs inhibits the development of Th1 and Th2 lymphocytes [ 47 ]. Moreover, in vitro COX-2 inhibition reduces B cell maturation and antibody production, with EP2 and EP4 receptors playing the most important role in the process as their agonists affect B cell activation [ 48 , 49 ].…”

Prostaglandin E2 receptor Ptger4b regulates female-specific peptidergic neurons and female sexual receptivity in medaka

“…Brain levels of PGE 2 and its metabolites, 15k-PGE 2 and dhk-PGE 2 , were measured by LC-MS/MS essentially as described elsewhere 51 . In brief, the brain samples were homogenized with methanol and solid phase extraction was performed using Oasis HLB extraction cartridges (Waters Corporation, Milford, MA).…”

Negative air ion exposure ameliorates depression-like behaviors induced by chronic mild stress in mice

“…Accumulated evidence supports the idea that stress leads to an increase of pro-inflammatory cytokines (Li et al 2016(Li et al , 2020. However, the data from animal models and clinical research revealed significant variabilities in type I and type II cytokine profiles (Cuervo et al 2021;Koivisto et al 2019;Razali et al 2020). It seems to be clear that the examination of a single cytokine or small groups of cytokines is not sufficient to evaluate the alterations of cytokines in depression-related animal models.…”