Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response
Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may pro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.655637/full |
| _version_ | 1818451288670601216 |
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| author | Lei Chu Chenhui Li Yongxing Li Qiuya Yu Huansha Yu Chunhui Li Wei Meng Juanjuan Zhu Quanyi Wang Chen Wang Shufang Cui |
| author_facet | Lei Chu Chenhui Li Yongxing Li Qiuya Yu Huansha Yu Chunhui Li Wei Meng Juanjuan Zhu Quanyi Wang Chen Wang Shufang Cui |
| author_sort | Lei Chu |
| collection | DOAJ |
| description | Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases. |
| first_indexed | 2024-12-14T21:04:49Z |
| format | Article |
| id | doaj.art-aa85f46cb4e74e5fa4f78e2a64375ccf |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T21:04:49Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aa85f46cb4e74e5fa4f78e2a64375ccf2022-12-21T22:47:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.655637655637Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon ResponseLei Chu0Chenhui Li1Yongxing Li2Qiuya Yu3Huansha Yu4Chunhui Li5Wei Meng6Juanjuan Zhu7Quanyi Wang8Chen Wang9Shufang Cui10State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaExperimental Animal Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, ChinaCyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases.https://www.frontiersin.org/articles/10.3389/fimmu.2021.655637/fullcyclic GMP-AMP synthase (cGAS)perillaldehydeherpes simplex virus type 1 (HSV-1)innate immunityautoimmune disease |
| spellingShingle | Lei Chu Chenhui Li Yongxing Li Qiuya Yu Huansha Yu Chunhui Li Wei Meng Juanjuan Zhu Quanyi Wang Chen Wang Shufang Cui Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response Frontiers in Immunology cyclic GMP-AMP synthase (cGAS) perillaldehyde herpes simplex virus type 1 (HSV-1) innate immunity autoimmune disease |
| title | Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response |
| title_full | Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response |
| title_fullStr | Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response |
| title_full_unstemmed | Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response |
| title_short | Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response |
| title_sort | perillaldehyde inhibition of cgas reduces dsdna induced interferon response |
| topic | cyclic GMP-AMP synthase (cGAS) perillaldehyde herpes simplex virus type 1 (HSV-1) innate immunity autoimmune disease |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.655637/full |
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