Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages
We previously isolated derrisfolin A, a novel rotenoid derivative, from the stems of Derris trifoliata Lour. (Leguminosae). Here, we report that derrisfolin A induces the expression of endogenous regucalcin (RGN) protein in both pancreatic MIN6 β‐cells and RAW264.7 macrophages. Induction of RGN expr...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13321 |
| _version_ | 1818974224078864384 |
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| author | Tomiyasu Murata Kazunori Hashimoto Susumu Kohno Chiaki Takahashi Masayoshi Yamaguchi Chihiro Ito Itoigawa Masataka Roji Kojima Kiyomi Hikita Norio Kaneda |
| author_facet | Tomiyasu Murata Kazunori Hashimoto Susumu Kohno Chiaki Takahashi Masayoshi Yamaguchi Chihiro Ito Itoigawa Masataka Roji Kojima Kiyomi Hikita Norio Kaneda |
| author_sort | Tomiyasu Murata |
| collection | DOAJ |
| description | We previously isolated derrisfolin A, a novel rotenoid derivative, from the stems of Derris trifoliata Lour. (Leguminosae). Here, we report that derrisfolin A induces the expression of endogenous regucalcin (RGN) protein in both pancreatic MIN6 β‐cells and RAW264.7 macrophages. Induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in MIN6 cells and RAW264.7 macrophages significantly decreased lipopolysaccharide (LPS)‐induced mRNA expression of Nos2, Il1b, and Tnf via nuclear factor‐κB activation; reduced LPS‐induced apoptosis in MIN6 cells, accompanied by decreased production of nitric oxide, interleukin‐1β, and tumor necrosis factor‐α; and attenuated generation of LPS‐induced reactive oxygen species, malondialdehyde, and 3‐nitrotyrosine in MIN6 cells. Additionally, in co‐cultures of MIN6 cells with RAW264.7 macrophages in the presence of LPS, induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in RAW264.7 macrophages attenuated apoptosis and oxidative/nitrosative stress in MIN6 cells. These results suggest that the induction of RGN expression in MIN6 cells was effective in suppressing LPS‐induced inflammatory cytotoxicity and that in co‐culture conditions, the induction of RGN expression in RAW264.7 macrophages blocked LPS‐induced paracrine effects of RAW264.7 macrophages on inflammatory cytotoxicity in MIN6 cells. Our findings suggest that derrisfolin A, a chemical inducer of RGN, might be useful for developing a new drug against macrophage‐associated β‐cell inflammation in type 2 diabetes. |
| first_indexed | 2024-12-20T15:36:39Z |
| format | Article |
| id | doaj.art-baf86eeca3ab4a7ab2eab73513c8ef84 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-20T15:36:39Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-baf86eeca3ab4a7ab2eab73513c8ef842022-12-21T19:35:23ZengWileyFEBS Open Bio2211-54632022-01-0112117519110.1002/2211-5463.13321Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophagesTomiyasu Murata0Kazunori Hashimoto1Susumu Kohno2Chiaki Takahashi3Masayoshi Yamaguchi4Chihiro Ito5Itoigawa Masataka6Roji Kojima7Kiyomi Hikita8Norio Kaneda9Laboratory of Molecular Biology Faculty of Pharmacy Meijo University Nagoya JapanLaboratory of Molecular Biology Faculty of Pharmacy Meijo University Nagoya JapanDivision of Oncology and Molecular Biology Cancer Research Institute Kanazawa University JapanDivision of Oncology and Molecular Biology Cancer Research Institute Kanazawa University JapanCancer Biology Program University of Hawaii Cancer Center University of Hawaii at Manoa Honolulu HI USALaboratory of Natural Products Chemistry Faculty of Pharmacy Meijo University Nagoya JapanSchool of Sport and Health Science Tokai Gakuen University Miyoshi JapanLaboratory of Analytical Pharmacy Faculty of Pharmacy Meijo University Nagoya JapanDepartment of Pharmacy Faculty of Pharmacy Gifu University of Medical Science Kani JapanLaboratory of Molecular Biology Faculty of Pharmacy Meijo University Nagoya JapanWe previously isolated derrisfolin A, a novel rotenoid derivative, from the stems of Derris trifoliata Lour. (Leguminosae). Here, we report that derrisfolin A induces the expression of endogenous regucalcin (RGN) protein in both pancreatic MIN6 β‐cells and RAW264.7 macrophages. Induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in MIN6 cells and RAW264.7 macrophages significantly decreased lipopolysaccharide (LPS)‐induced mRNA expression of Nos2, Il1b, and Tnf via nuclear factor‐κB activation; reduced LPS‐induced apoptosis in MIN6 cells, accompanied by decreased production of nitric oxide, interleukin‐1β, and tumor necrosis factor‐α; and attenuated generation of LPS‐induced reactive oxygen species, malondialdehyde, and 3‐nitrotyrosine in MIN6 cells. Additionally, in co‐cultures of MIN6 cells with RAW264.7 macrophages in the presence of LPS, induction of RGN expression by derrisfolin A or retrovirus‐mediated gene transfer in RAW264.7 macrophages attenuated apoptosis and oxidative/nitrosative stress in MIN6 cells. These results suggest that the induction of RGN expression in MIN6 cells was effective in suppressing LPS‐induced inflammatory cytotoxicity and that in co‐culture conditions, the induction of RGN expression in RAW264.7 macrophages blocked LPS‐induced paracrine effects of RAW264.7 macrophages on inflammatory cytotoxicity in MIN6 cells. Our findings suggest that derrisfolin A, a chemical inducer of RGN, might be useful for developing a new drug against macrophage‐associated β‐cell inflammation in type 2 diabetes.https://doi.org/10.1002/2211-5463.13321derrisfolin AinflammationlipopolysaccharideMIN6 cellsRAW264.7 macrophagesregucalcin |
| spellingShingle | Tomiyasu Murata Kazunori Hashimoto Susumu Kohno Chiaki Takahashi Masayoshi Yamaguchi Chihiro Ito Itoigawa Masataka Roji Kojima Kiyomi Hikita Norio Kaneda Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages FEBS Open Bio derrisfolin A inflammation lipopolysaccharide MIN6 cells RAW264.7 macrophages regucalcin |
| title | Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages |
| title_full | Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages |
| title_fullStr | Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages |
| title_full_unstemmed | Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages |
| title_short | Chemical inducer of regucalcin attenuates lipopolysaccharide‐induced inflammatory responses in pancreatic MIN6 β‐cells and RAW264.7 macrophages |
| title_sort | chemical inducer of regucalcin attenuates lipopolysaccharide induced inflammatory responses in pancreatic min6 β cells and raw264 7 macrophages |
| topic | derrisfolin A inflammation lipopolysaccharide MIN6 cells RAW264.7 macrophages regucalcin |
| url | https://doi.org/10.1002/2211-5463.13321 |
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