• Animal Bioscience
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• 제36권1호
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• pp.156-166
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• 2023

Objective: In this study, we investigated the effects of Rubus coreanus-derived lactic acid bacteria (LAB) fermented feed (RC-LAB fermented feed) and three types of LAB (Lactobacillus plantarum, Lactobacillus acidophilus, Bifidobacterium animalis) on the expression of transcription factors and cytokines in Th1, Th2, Th17, and Treg cells in the intestinal lymph nodes and spleens of rats. In addition, the effect on intestinal microbiota composition and body weight was investigated. Methods: Five-week-old male rats were assigned to five treatments and eight replicates. The expression of transcription factors and cytokines of Th1, Th2, Th17, and Treg cells in the intestinal lymph nodes and spleens was analyzed using real-time reverse transcriptase polymerase chain reaction assays. Intestinal tract microbiota compositions were analyzed by next-generation sequencing and quantitative polymerase chain reaction assays. Results: RC-LAB fermented feed and three types of LAB increased the expression of transcription factors and cytokines in Th1, Treg cells and Galectin-9, but decreased in Th2 and Th17 cells. In addition, the intestinal microbiota composition changed, the body weight and Firmicutes to Bacteroidetes (F/B) ratio decreased, and the relative abundance of LAB increased. Conclusion: LAB fermented feed and three types of LAB showed an immune modulation effect by inducing T cell polarization and increased LAB in the intestinal microbiota.

• Environmental Analysis Health and Toxicology
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• 제17권4호
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• pp.325-332
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• 2002

A helper T(Th)1-mediated response is known to enhance cell -mediated immunity, while a Th2-mediated response is associated with the humoral immunity that if elevated IgE levels and eosinophilia. Prostaglandin (PG)E$_2$results in the decreased capability of Iymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T Iymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGE$_2$pathway. The purpose of this study is to determine the effort of CPF on the in vitro production of Th cytokines and the role of PGE$_2$on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF(0.1, 1, 10 and 100$\mu$M) in the presence of absence of indomethacin or PGE$_2$for 12 h and then were incubated with concanavalin (Con) A for 48 h. These results showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the splenic IL-4 production at low doses (0.1 and 1$\mu$M) but did not affect at high doses (10 and 100 $\mu$M). Indomethacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose -dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 $\mu$M. High dose of CPF significantly reduced the PGE$_2$-decreased production of IL-2 and IFN-γ, while the PGE$_2$- induced production of IL-4 was significantly enhanced by CPF 1 $\mu$M. These findings suggest that CPF nay down-regulate the immune response of Th 1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Thl cytokines may not be mediated by endogenous PGE$_2$. Also, CPF may attenuate the exogenous PGE$_2$-decreased Th 1 immune response in a dose--dependent manner but may affect dose-independently the PGE$_2$-induced Th2 immune response.

• The Korean Journal of Physiology and Pharmacology
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• 제23권4호
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• pp.251-261
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• 2019

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

• Food Science and Biotechnology
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• 제17권3호
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• pp.631-636
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• 2008

Acanthopanax divaricatus var. albeofructus (ADA) have been shown to have various levels of activity such as antioxidant, anticancer, antivirus, and immunostimulatory effects. However, little is known about its mechanism related to the modulation of immune activities. In this study, a water extract of ADA leaves were used to treat human peripheral blood mononuclear cells (hPBMC) to determine the underlying mechanisms for the immunostimulatory effects. To characterize its immunomodulatory activity, the secretion level of various cytokines including IL-2, IL-4, IL-6, IL-10, IL-12, IFN-$\gamma$, and TNF-$\alpha$ were measured using enzyme-linked immunosorbent assay (ELISA). Treatment of hPBMC with ADA leaf extract in an in vitro experiment induced various Th1 cytokines in a dose-dependent manner. A significant increase of IL-2, IL-12, IFN-$\gamma$, and TNF-$\alpha$ secretion was observed in the presence of ADA leaf extract. In contrast, Th2 cytokines including IL-4 and IL-6 were suppressed. There was no significant change in IL-10 release. Our results showed an increase in Th1 and a decrease in Th2 cytokine secretion which suggests that ADA may influence the immune response towards a predominance of Th1 cytokines in the immune system.

• IMMUNE NETWORK
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• 제10권1호
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• pp.1-4
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• 2010

Asthma is characterized by chronic airway inflammation with intense eosinophil and lymphocyte infiltration, mucus hyperproduction, and airway hyperresponsiveness. Accumulating evidence indicates that antigen-specific Th2 cells and their cytokines such as IL-4, IL-5, and IL-13 orchestrate these pathognomonic features of asthma. In addition, we and others have recently shown that IL-17-producing $CD4^+$ T cells (Th17 cells) and IL-23, an IL-12-related cytokine that is essential for survival and functional maturation of Th17 cells, are involved in antigen-induced airway inflammation. In this review, our current understanding of the roles of IL-23 and Th17 cells in the pathogenesis of allergic airway inflammation will be summarized.

• Clinical and Experimental Reproductive Medicine
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• 제24권3호
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• pp.399-405
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• 1997

Progesterone is necessary for successful pregnancy and had immunosuppressive properties. Peripheral blood mononuclear cells (PBMC) from many women with unexplained recurrent spontaneous abortion responded to trophoblast extract in vitro by prolifertion and releasing soluble, heat-labile factors that are toxic to mouse embryos (embryotoxic factors). Accumulating evidence suggests that T Helper (Th)-1 type immunity to trophoblast is correlated with embryotoxic factor production and is associated with pregnancy loss, while Th2-type immunity is associated with successful gestation. The objective of this study was to determine whether progesterone can inhibit Th1-type cytokine secretion (IFN-${\gamma}$, TNF-${\alpha}$) by trophoblast-activated peripheral blood mononuclear cells from 23 nonpregnant women (age 25-35) with unexplained recurrent abortion (median 5, range 3 to 15)who otherwise produce embryotoxic factors in response to trophoblast. We also determined whether progesterone affected Th2-type cytokines (IL-4, IL-10) in this system in vitro and if IL-10 (1,500 pg/mL) could inhibit Th1-type immunity to trophoblast. IFN-${\gamma}$ was detected in 17 of 23 (74%) trophoblast stimulated PBMC culture supernatants ($77.94{\pm}23.79$ pg/mL) containing embryotoxic activity. TNF-${\alpha}$ was detected in 19 (83%) of these same supernatants ($703.15{\pm}131.36$ pg/mL). In contrast, none of the supernatants contained detectable levels of IL-4 or IL-10. Progesterone ($10^{-5}$, $10^{-7}$, $10^{-9}$M) inhibited Th1-type immunity in a dose dependent manner, but had no effect on Th2-type cytokine secretion. The inhibitory effects of progesterone were abrogated with RU486, but did not affect Th2-type cytokine secretion in trophoblast-activated cell cultures. IL-10, like progesterone also inhibited Th1-type cytokine secretion but had no effect on Th2-type cytokines. These data suggest that therapies designed to suppress Th1-type cytokine secretion in women with recurrent abortion who have evidence of Th1-type immunity to trophoblast may be efficacious in preventing pregnancy loss and should be tested in appropriately designed clinical trials.

• IMMUNE NETWORK
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• 제24권2호
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• pp.14.1-14.26
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• 2024

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

• Molecules and Cells
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• 제44권5호
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• pp.318-327
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• 2021

CD4+ T helper (Th) cells play a crucial role in the modulation of innate and adaptive immune responses through the differentiation of Th precursor cells into several subsets, including Th1, Th2, Th17, and regulatory T (Treg) cells. Effector Th and Treg cells are distinguished by the production of signature cytokines and are important for eliminating intracellular and extracellular pathogens and maintaining immune homeostasis. Stimulation of naive Th cells by T cell receptor and specific cytokines activates master transcription factors and induces lineage specification during the differentiation of Th cells. The master transcription factors directly activate the transcription of signature cytokine genes and also undergo post-translational modifications to fine-tune cytokine production and maintain immune balance through cross-regulation with each other. This review highlights the post-translational modifications of master transcription factors that control the differentiation of effector Th and Treg cells and provides additional insights on the immune regulation mediated by protein argininemodifying enzymes in effector Th cells.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.388-394
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• 2009

The cytokines which is produced by allergen-specific T helper (Th) cells play a pivotal role in the pathogenesis of asthma. Asthma is caused by exaggerated T-helper 2 (Th2)-based immune responses. It is suggested that controlling such Th2-based response is necessary for asthma therapy. The current therapies for asthma focus primarily on control of symptoms and suppression of inflammation, without affecting the underlying cause. So, we examined that anti-asthmatic drugs might have play a certain role in Th2/Th1 balance. Splenocytes isolated from ovalbumin (OVA)-sensitized mice cultured with anti-asthmatic drugs. It is well known that Th2 and Th1 immune responses can balance one another, as Th2 mediators suppress Th1 responses and Th1 mediators similarly inhibit Th2 responses. But salmeterol inhibits both of Th1 and Th2 mediators, which salmeterol is a suppressor of immune responses not only a suppressor of Th2-based immune responses. Aminophylline is a weak suppressor of immune responses. But ipratropium and cromoglycate don't have any suppressor effect to Th2-driven responses. They only have suppressor effect to Th1 immune responses. Salmeterol, ipratropium, aminophylline, and cromoglycate augmented mRNA levels of CRTH2, EP2, and IP2 receptors in OVA-sensitized splenocytes. It is well known that the up-regulation of CRTH2 - $PGD_2$ receptor - results in restraint of eosinophil recruitment and that the increment of IP and EP2 - $PGI_2$ and $PGE_2$ receptor, respectively - may induce the accumulation of cAMP that decrease the effector function of T cells. Moreover salmeterol and cromoglycate increase the mRNA expression of $PGD_2$ synthase. These findings indicate that anti-asthma agents may alleviate the immunological responses that cause the asthmatic diseases.

• Journal of Microbiology and Biotechnology
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• 제26권3호
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• pp.469-476
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• 2016

This study was undertaken to evaluate the immunomodulatory effect of dead nano-sized Lactobacillus plantarum (nLp) in RAW 264.7 cells and murine primary splenocytes. nLp is a dead, shrunken, processed form of L. plantarum nF1 isolated from kimchi (a traditional Korean fermented cabbage) and is less than 1 μm in size. It was found that nLp treatment stimulated nitric oxide (NO) production more in RAW 264.7 macrophages than pure live L. plantarum (pLp), and that the stimulatory properties were probably largely derived from its cell wall. In addition, nLp induced murine splenocyte proliferation more so than pLp; in particular, a high dose of nLp (1.0 × 10¹¹ CFU/ml) stimulated proliferation as much as lipopolysaccharide at 2 μg/ml. Moreover, according to our cytokine profile results in splenocytes, nLp treatment promoted Th1 (TNF-α, IL-12 p70) responses rather than Th2 (IL-4, IL-5) responses and also increased Th17 (IL-6, IL-17A) responses. Thus, nLp stimulated NO release in RAW 264.7 cells and induced splenocyte proliferation more so than pLp and stimulated Th1 and Th17 cytokine production. These findings suggested that dead nLp has potential use as a functional food ingredient to improve the immune response, and especially as a means of inducing Th1/Th17 immune responses.