α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages
α-Viniferin, an oligostilbene of trimeric resveratrol, has been reported to have antiinflammatory potential in carrageenin-induced paw edema or adjuvant-induced arthritis in animal models. However, little is known about the molecular basis. In this study, α-viniferin at 3 – 10 μM dose-dependently in...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319309752 |
| _version_ | 1818511600712155136 |
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| author | Eun Yong Chung Eunmiri Roh Jeong-Ah Kwak Heun-Sik Lee Seung Ho Lee Chong-Kil Lee Sang-Bae Han Youngsoo Kim |
| author_facet | Eun Yong Chung Eunmiri Roh Jeong-Ah Kwak Heun-Sik Lee Seung Ho Lee Chong-Kil Lee Sang-Bae Han Youngsoo Kim |
| author_sort | Eun Yong Chung |
| collection | DOAJ |
| description | α-Viniferin, an oligostilbene of trimeric resveratrol, has been reported to have antiinflammatory potential in carrageenin-induced paw edema or adjuvant-induced arthritis in animal models. However, little is known about the molecular basis. In this study, α-viniferin at 3 – 10 μM dose-dependently inhibited interferon (IFN)-γ–induced Ser727 phosphorylation of the signal transducer and activation of transcription-1 (STAT-1), a pivotal transcription factor controlling IFN-γ–targeted genes, in RAW 264.7 macrophages, and also IFN-γ–induced activation of the extracellular signal-regulated kinase (ERK)-1, a protein kinase upstream of the Ser727 phosphorylation of STAT-1. However, α-viniferin, only at a higher concentration of 10 μM, inhibited Janus kinase 2–mediated Tyr701 phosphorylation of STAT-1 in the cells. To understand STAT-1–dependent inflammatory responses, we quantified nitric oxide (NO) or chemokines. α-Viniferin at 3 – 10 μM dose-dependently inhibited IFN-γ–induced production of NO, IFN-γ–inducible protein-10 (IP-10), or the monokine induced by IFN-γ (MIG) in RAW 264.7 cells and also that of NO in primary macrophages-derived from C57BL/6 mice. Furthermore, α-viniferin diminished IFN-γ–induced protein levels of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10, or MIG as well as inhibited promoter activity of the iNOS gene. In conclusion, this study proposes an antiinflammatory mechanism of α-viniferin, down-regulating STAT-1–inducible inflammatory genes via inhibiting ERK-mediated STAT-1 activation in IFN-γ–stimulated macrophages. Keywords:: α-viniferin, anti-inflammation, signal transducer and activation of transcription-1 (STAT-1) activation, interferon (IFN)-γ, macrophage |
| first_indexed | 2024-12-10T23:35:19Z |
| format | Article |
| id | doaj.art-273f5817d6df49318808300655993828 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T23:35:19Z |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-273f5817d6df493188083006559938282022-12-22T01:29:12ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011124405414α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated MacrophagesEun Yong Chung0Eunmiri Roh1Jeong-Ah Kwak2Heun-Sik Lee3Seung Ho Lee4Chong-Kil Lee5Sang-Bae Han6Youngsoo Kim7College of Pharmacy, Chungbuk National University, Cheongju 361-763, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, KoreaCollege of Pharmacy, Yeungnam University, Kyeongsan 712-749, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, KoreaCollege of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea; Corresponding author. youngsoo@chungbuk.ac.krα-Viniferin, an oligostilbene of trimeric resveratrol, has been reported to have antiinflammatory potential in carrageenin-induced paw edema or adjuvant-induced arthritis in animal models. However, little is known about the molecular basis. In this study, α-viniferin at 3 – 10 μM dose-dependently inhibited interferon (IFN)-γ–induced Ser727 phosphorylation of the signal transducer and activation of transcription-1 (STAT-1), a pivotal transcription factor controlling IFN-γ–targeted genes, in RAW 264.7 macrophages, and also IFN-γ–induced activation of the extracellular signal-regulated kinase (ERK)-1, a protein kinase upstream of the Ser727 phosphorylation of STAT-1. However, α-viniferin, only at a higher concentration of 10 μM, inhibited Janus kinase 2–mediated Tyr701 phosphorylation of STAT-1 in the cells. To understand STAT-1–dependent inflammatory responses, we quantified nitric oxide (NO) or chemokines. α-Viniferin at 3 – 10 μM dose-dependently inhibited IFN-γ–induced production of NO, IFN-γ–inducible protein-10 (IP-10), or the monokine induced by IFN-γ (MIG) in RAW 264.7 cells and also that of NO in primary macrophages-derived from C57BL/6 mice. Furthermore, α-viniferin diminished IFN-γ–induced protein levels of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10, or MIG as well as inhibited promoter activity of the iNOS gene. In conclusion, this study proposes an antiinflammatory mechanism of α-viniferin, down-regulating STAT-1–inducible inflammatory genes via inhibiting ERK-mediated STAT-1 activation in IFN-γ–stimulated macrophages. Keywords:: α-viniferin, anti-inflammation, signal transducer and activation of transcription-1 (STAT-1) activation, interferon (IFN)-γ, macrophagehttp://www.sciencedirect.com/science/article/pii/S1347861319309752 |
| spellingShingle | Eun Yong Chung Eunmiri Roh Jeong-Ah Kwak Heun-Sik Lee Seung Ho Lee Chong-Kil Lee Sang-Bae Han Youngsoo Kim α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages Journal of Pharmacological Sciences |
| title | α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages |
| title_full | α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages |
| title_fullStr | α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages |
| title_full_unstemmed | α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages |
| title_short | α-Viniferin Suppresses the Signal Transducer and Activation of Transcription-1 (STAT-1)–Inducible Inflammatory Genes in Interferon-γ–Stimulated Macrophages |
| title_sort | α viniferin suppresses the signal transducer and activation of transcription 1 stat 1 inducible inflammatory genes in interferon γ stimulated macrophages |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319309752 |
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