Biology subjects

Yashiro, T.

Publications and source records attributed to Yashiro, T..

5 recordsLinked to original sources

bioRxiv2023

The gut lactic acid bacteria metabolite, 10-oxo-cis-6,trans-11-octadecadienoic acid, suppresses inflammatory bowel disease in mice by modulating the NRF2 pathway and GPCR-signaling

Various gut bacteria, including Lactobacillus plantarum, possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo-cis-6,trans-11-octadecadienoic acid ({gamma}KetoC), a {gamma}-linolenic acid (GLA)-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and LPS-induced production of inflammatory cytokines. The treatment with {gamma}KetoC significantly suppressed proliferation of CD4+ T cells, LPS-induced activation of bone marrow-derived dendritic cells (BMDCs), and LPS-induced IL-6 release from peritoneal cells, splenocytes, and CD11c+ cells isolated from the spleen. {gamma}KetoC also inhibited the release of inflammatory cytokines from BMDCs stimulated with poly-I:C, R-848, or CpG. Further in vitro experiments using an agonist of GPR40/120 suggested the involvement of these GPCRs in the effects of {gamma}KetoC on DCs. We also found that {gamma}KetoC stimulated the NRF2 pathway in DCs, and the suppressive effects of {gamma}KetoC and agonist of GPR40/120 on the release of IL-6 and IL-12 were reduced in Nrf2-/- BMDCs. We evaluated the role of NRF2 in the anti-inflammatory effects of {gamma}KetoC in a dextran sodium sulfate-induced colitis model. The oral administration of {gamma}KetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6 and Nrf2+/- mice with colitis. In contrast, the pathology of colitis was deteriorated in Nrf2-/- mice even with the administration of {gamma}KetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway and GPCRs in {gamma}KetoC-mediated anti-inflammatory responses.

immunology↗

bioRxiv2023

Butyrate, valerate, and niacin ameliorate anaphylaxis by suppressing IgE-dependent mast cell activation: Roles of GPR109A, PGE2, and epigenetic regulation

Short chain fatty acids (SCFAs) were recently shown to modulate the development and functions of immune-related cells. However, the molecular mechanisms by which SCFAs regulate mast cells (MCs) are not fully understood. We found that the oral administration of valerate or butyrate ameliorated passive systemic anaphylaxis in mice. Butyrate and valerate suppressed the IgE-mediated degranulation of bone marrow-derived MCs, which were eliminated by pertussis toxin and by the knockdown of Gpr109a. A treatment with trichostatin A suppressed IgE-mediated MC activation and reduced the surface expression level of Fc{varepsilon}RI on MCs. Acetylsalicylic acid and indomethacin attenuated the suppressive effects of SCFAs on degranulation. The degranulation degree was significantly decreased by the treatment with PGE2 whose release from MCs was markedly enhanced by SCFAs. The SCFA-mediated amelioration of anaphylaxis was exacerbated by COX inhibitors and an EP3 antagonist. The administration of niacin, a ligand of GPR109A, alleviated the symptoms of passive cutaneous anaphylaxis, which was inhibited by COX inhibitors and the EP3 antagonist. Key MessagesShort chain fatty acids (SCFAs), particularly butyrate and valerate, suppress the IgE-mediated activation of mast cells (MCs) in vivo and in vitro. SCFAs enhance the release of PGE2 from MCs, which inhibits the IgE-mediated activation of MCs. Niacin, a ligand of GPR109A, ameliorates IgE-dependent anaphylaxis. The administration of COX inhibitors or an antagonist of PGE2 receptor 3 (EP3) inhibited the suppressive effects of butyrate and niacin on IgE-dependent anaphylaxis.

immunology↗

bioRxiv2023

Kaempferol suppresses the activation of mast cells by modulating the expression of FcϵRI and SHIP1

In the present study, we evaluated the effects of kaempferol on bone marrow-derived mast cells (BMMCs). Kaempferol treatment significantly and dose-dependently inhibited IgE-induced degranulation, and cytokine production of BMMCs under the condition that cell viability was maintained. Kaempferol downregulated the surface expression levels of Fc{varepsilon}RI on BMMCs, but the mRNA levels of Fc{varepsilon}RI, {beta}, and {gamma}-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface Fc{varepsilon}RI on BMMCs was still observed in the presence of a protein-synthesis inhibitor. These results suggest that kaempferol reduced the surface Fc{varepsilon}RI on BMMCs, independently of transcription and translation. We also found that kaempferol inhibited both LPS- and IL-33-induced IL-6 production from BMMCs, without affecting the expression levels of their receptors, TLR4 and ST2. Although kaempferol treatment increased the protein amount of NRF2, a master transcription factor of antioxidant stress, in BMMCs, inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we observed that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating Fc{varepsilon}RI and upregulating SHIP1, and the SHIP1 increase is involved in the suppression of various signaling-mediated stimulations of BMMCs, such as those associated with TLR4 and ST2.

immunology↗

bioRxiv2023

Immunostimulatory effects of Bacillus coagulans SANK70258

Specific intestinal bacteria modulate immunoresponses through various pathways, and several probiotic bacteria have been identified as immunostimulants by screening. In the present study, we evaluated the immunomodulating effects of Bacillus coagulans SANK70258 (B. coagulans SANK70258), a spore-forming and lactic acid-producing bacterium usable as food supplement for human and animals. We found that treatment of mouse splenocytes with {gamma}-ray irradiated B. coagulans SANK70258 induced high amount of IFN-{gamma} in comparison with 7 kinds of typical lactic acid bacteria. Further analyses using splenocytes revealed that NK cell is a major source of IFN-{gamma}, and B. coagulans SANK70258-induced IFN-{gamma} production was inhibited by neutralization of IL-12 or IL-23, depletion of CD11c+ cells, and inhibition of NF{kappa}B. B. coagulans SANK70258 also induced release of IFN-{gamma} from activated CD8+ T cells, and increased expression of chemokine receptors in CD8+ T cells. B. coagulans SANK70258-treatment induced production of cytokines from bone marrow-derived dendritic cells, which is reduced by knockdown of Tlr2 and Nod2. B. coagulans SANK70258-treatment also induced IgA production from Peyers patch cells with high level among tested lactic bacteria. The oral intake of {gamma}-ray irradiated B. coagulans SANK70258 significantly increased intestinal IgA levels and IgA-expressing B cells in the Peyers patch of mice. Taken together, we conclude that B. coagulans SANK70258 possesses high activity as immunostimulant inducing production of IFN-{gamma} and IgA.

immunology↗

bioRxiv2022

Rose flavor compound β-damascone regulates dendritic cell-mediated immunoresponses by modulating the NRF2 pathway and ameliorates contact hypersensitivity

Dendritic cells (DCs), which are typical antigen-presenting cells, localize to various sites in the body, particularly the front line of infection as sentinels, and are involved in innate and adaptive immune responses. Although the functions of DCs, such as pathogen-induced cytokine production and antigen-specific T cell activation, are important for host defenses against infection and tumorigenesis, the hyper- and/or extended activation of DCs leads to inflammatory and autoimmune diseases. In the present study, {beta}-damascone, a major ingredient of rose fragrance, was selected from an aroma library as a candidate compound that suppresses antigen-induced immune responses. {beta}-Damascone inhibited the functions of DCs, including the antigen-dependent proliferation of T cells, DC-induced Th1 development, and the TLR ligand-induced production of inflammatory cytokines by DCs. The {beta}-damascone treatment also increased the protein level of the transcription factor NRF2, which plays key roles in antioxidant responses, and the transcription of Hmox1, a target gene of NRF2, in DCs. Nrf2-/- DCs induced Th1-development and produced large amount of IL-12p40 even in the presence of {beta}-damascone, whereas these functions by Nrf2+/- DCs were inhibited by {beta}-damascone under the same conditions. The intake of {beta}-damascone suppressed ear swelling in contact hypersensitivity (CHS) model mice, but not in CHS-induced Nrf2-/- mice. Collectively, the present results indicate the potential of the rose aroma compound {beta}-damascone, which suppresses DC-mediated immune responses by activating the NRF2 pathway in DCs, for the prevention and/or attenuation of immune-mediated diseases.

immunology↗