Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A
Staphylococcal enterotoxin A (SEA), which is a superantigen toxin protein, binds to cytokine receptor gp130. Gp130 activates intracellular signaling pathways, including the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The effects of SEA on the JAK/STAT signalin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/9/609 |
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| author | Yuko Shimamura Rina Noaki Ami Kurokawa Mio Utsumi Chikako Hirai Toshiyuki Kan Shuichi Masuda |
| author_facet | Yuko Shimamura Rina Noaki Ami Kurokawa Mio Utsumi Chikako Hirai Toshiyuki Kan Shuichi Masuda |
| author_sort | Yuko Shimamura |
| collection | DOAJ |
| description | Staphylococcal enterotoxin A (SEA), which is a superantigen toxin protein, binds to cytokine receptor gp130. Gp130 activates intracellular signaling pathways, including the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The effects of SEA on the JAK/STAT signaling pathway in mouse spleen cells were examined. After treatment with SEA, mRNA expression levels of interferon gamma (IFN-γ) and suppressor of cytokine-signaling 1 (SOCS1) increased. SEA-induced IFN-γ and SOCS1 expression were decreased by treatment with (−)-epigallocatechin gallate (EGCG). The phosphorylated STAT3, Tyr705, increased significantly in a SEA concentration-dependent manner in mouse spleen cells. Although (−)-3″-Me-EGCG did not inhibit SEA-induced phosphorylated STAT3, EGCG and (−)-4″-Me-EGCG significantly inhibited SEA-induced phosphorylated STAT3. It was thought that the hydroxyl group at position 3 of the galloyl group in the EGCG was responsible for binding to SEA and suppressing SEA-induced phosphorylation of STAT3. Through protein thermal shift assay in vitro, the binding of the gp130 receptor to SEA and the phosphorylation of STAT3 were inhibited by the interaction between EGCG and SEA. As far as we know, this is the first report to document that EGCG inhibits the binding of the gp130 receptor to SEA and the associated phosphorylation of STAT3. |
| first_indexed | 2024-03-10T07:09:28Z |
| format | Article |
| id | doaj.art-414c817d55c944099ae61871bacedfed |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T07:09:28Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-414c817d55c944099ae61871bacedfed2023-11-22T15:30:54ZengMDPI AGToxins2072-66512021-08-0113960910.3390/toxins13090609Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin AYuko Shimamura0Rina Noaki1Ami Kurokawa2Mio Utsumi3Chikako Hirai4Toshiyuki Kan5Shuichi Masuda6School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanDepartment of Synthetic Organic & Medicinal Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanSchool of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, JapanStaphylococcal enterotoxin A (SEA), which is a superantigen toxin protein, binds to cytokine receptor gp130. Gp130 activates intracellular signaling pathways, including the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The effects of SEA on the JAK/STAT signaling pathway in mouse spleen cells were examined. After treatment with SEA, mRNA expression levels of interferon gamma (IFN-γ) and suppressor of cytokine-signaling 1 (SOCS1) increased. SEA-induced IFN-γ and SOCS1 expression were decreased by treatment with (−)-epigallocatechin gallate (EGCG). The phosphorylated STAT3, Tyr705, increased significantly in a SEA concentration-dependent manner in mouse spleen cells. Although (−)-3″-Me-EGCG did not inhibit SEA-induced phosphorylated STAT3, EGCG and (−)-4″-Me-EGCG significantly inhibited SEA-induced phosphorylated STAT3. It was thought that the hydroxyl group at position 3 of the galloyl group in the EGCG was responsible for binding to SEA and suppressing SEA-induced phosphorylation of STAT3. Through protein thermal shift assay in vitro, the binding of the gp130 receptor to SEA and the phosphorylation of STAT3 were inhibited by the interaction between EGCG and SEA. As far as we know, this is the first report to document that EGCG inhibits the binding of the gp130 receptor to SEA and the associated phosphorylation of STAT3.https://www.mdpi.com/2072-6651/13/9/609staphylococcal enterotoxin Agp130STAT3(−)-epigallocatechin gallate |
| spellingShingle | Yuko Shimamura Rina Noaki Ami Kurokawa Mio Utsumi Chikako Hirai Toshiyuki Kan Shuichi Masuda Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A Toxins staphylococcal enterotoxin A gp130 STAT3 (−)-epigallocatechin gallate |
| title | Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A |
| title_full | Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A |
| title_fullStr | Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A |
| title_full_unstemmed | Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A |
| title_short | Effect of (−)-Epigallocatechin Gallate on Activation of JAK/STAT Signaling Pathway by Staphylococcal Enterotoxin A |
| title_sort | effect of epigallocatechin gallate on activation of jak stat signaling pathway by staphylococcal enterotoxin a |
| topic | staphylococcal enterotoxin A gp130 STAT3 (−)-epigallocatechin gallate |
| url | https://www.mdpi.com/2072-6651/13/9/609 |
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