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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 dow...

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Autores principales: Nagata, Kazuki, Araumi, Sanae, Ando, Daisuke, Ito, Naoto, Ando, Miki, Ikeda, Yuki, Takahashi, Miki, Noguchi, Sakura, Yasuda, Yayoi, Nakano, Nobuhiro, Ando, Tomoaki, Hara, Mutsuko, Yashiro, Takuya, Hachisu, Masakazu, Nishiyama, Chiharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059252/
https://www.ncbi.nlm.nih.gov/pubmed/36983066
http://dx.doi.org/10.3390/ijms24065997
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author Nagata, Kazuki
Araumi, Sanae
Ando, Daisuke
Ito, Naoto
Ando, Miki
Ikeda, Yuki
Takahashi, Miki
Noguchi, Sakura
Yasuda, Yayoi
Nakano, Nobuhiro
Ando, Tomoaki
Hara, Mutsuko
Yashiro, Takuya
Hachisu, Masakazu
Nishiyama, Chiharu
author_facet Nagata, Kazuki
Araumi, Sanae
Ando, Daisuke
Ito, Naoto
Ando, Miki
Ikeda, Yuki
Takahashi, Miki
Noguchi, Sakura
Yasuda, Yayoi
Nakano, Nobuhiro
Ando, Tomoaki
Hara, Mutsuko
Yashiro, Takuya
Hachisu, Masakazu
Nishiyama, Chiharu
author_sort Nagata, Kazuki
collection PubMed
description 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 FcεRI on BMMCs, but the mRNA levels of FcεRIα, β, and γ-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface FcεRI on BMMCs was still observed when protein synthesis or protein transporter was inhibited. 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 NF-E2-related factor 2 (NRF2)—a master transcription factor of antioxidant stress—in BMMCs, the inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we found that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. The kaempferol-induced upregulation of SHIP1 was also observed in peritoneal MCs. The knockdown of SHIP1 by siRNA significantly enhanced IgE-induced degranulation of BMMCs. A Western blotting analysis showed that IgE-induced phosphorylation of PLCγ was suppressed in kaempferol-treated BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating FcεRI 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.
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spelling pubmed-100592522023-03-30 Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1 Nagata, Kazuki Araumi, Sanae Ando, Daisuke Ito, Naoto Ando, Miki Ikeda, Yuki Takahashi, Miki Noguchi, Sakura Yasuda, Yayoi Nakano, Nobuhiro Ando, Tomoaki Hara, Mutsuko Yashiro, Takuya Hachisu, Masakazu Nishiyama, Chiharu Int J Mol Sci Article 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 FcεRI on BMMCs, but the mRNA levels of FcεRIα, β, and γ-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface FcεRI on BMMCs was still observed when protein synthesis or protein transporter was inhibited. 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 NF-E2-related factor 2 (NRF2)—a master transcription factor of antioxidant stress—in BMMCs, the inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we found that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. The kaempferol-induced upregulation of SHIP1 was also observed in peritoneal MCs. The knockdown of SHIP1 by siRNA significantly enhanced IgE-induced degranulation of BMMCs. A Western blotting analysis showed that IgE-induced phosphorylation of PLCγ was suppressed in kaempferol-treated BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating FcεRI 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. MDPI 2023-03-22 /pmc/articles/PMC10059252/ /pubmed/36983066 http://dx.doi.org/10.3390/ijms24065997 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nagata, Kazuki
Araumi, Sanae
Ando, Daisuke
Ito, Naoto
Ando, Miki
Ikeda, Yuki
Takahashi, Miki
Noguchi, Sakura
Yasuda, Yayoi
Nakano, Nobuhiro
Ando, Tomoaki
Hara, Mutsuko
Yashiro, Takuya
Hachisu, Masakazu
Nishiyama, Chiharu
Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
title Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
title_full Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
title_fullStr Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
title_full_unstemmed Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
title_short Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1
title_sort kaempferol suppresses the activation of mast cells by modulating the expression of fcεri and ship1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059252/
https://www.ncbi.nlm.nih.gov/pubmed/36983066
http://dx.doi.org/10.3390/ijms24065997
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