NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton
AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigat...
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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/354843 |
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| _version_ | 1832548653233864704 |
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| author | Van Thai Ha Heung Soo Beak Eunji Kim Kwang-Soo Baek Muhammad Jahangir Hossen Woo Seok Yang Yong Kim Jun Ho Kim Sungjae Yang Jeong-Hwan Kim Yung Hyup Joo Chang Seok Lee Joonho Choi Hong-Ju Shin Sungyoul Hong Song Seok Shin Jae Youl Cho |
| author_facet | Van Thai Ha Heung Soo Beak Eunji Kim Kwang-Soo Baek Muhammad Jahangir Hossen Woo Seok Yang Yong Kim Jun Ho Kim Sungjae Yang Jeong-Hwan Kim Yung Hyup Joo Chang Seok Lee Joonho Choi Hong-Ju Shin Sungyoul Hong Song Seok Shin Jae Youl Cho |
| author_sort | Van Thai Ha |
| collection | DOAJ |
| description | AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2 production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2 in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1β in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBα and IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBα and AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation. |
| format | Article |
| id | doaj-art-07f143d337e048f38be3c4a531e8c583 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-07f143d337e048f38be3c4a531e8c5832025-02-03T06:13:26ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/354843354843NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane SkeletonVan Thai Ha0Heung Soo Beak1Eunji Kim2Kwang-Soo Baek3Muhammad Jahangir Hossen4Woo Seok Yang5Yong Kim6Jun Ho Kim7Sungjae Yang8Jeong-Hwan Kim9Yung Hyup Joo10Chang Seok Lee11Joonho Choi12Hong-Ju Shin13Sungyoul Hong14Song Seok Shin15Jae Youl Cho16Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaMedical Beauty Research Institute, AmorePacific R&D Center, Yongin 446-729, Republic of KoreaDepartment of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of KoreaAP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2 production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2 in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1β in LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBα and IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBα and AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation.http://dx.doi.org/10.1155/2014/354843 |
| spellingShingle | Van Thai Ha Heung Soo Beak Eunji Kim Kwang-Soo Baek Muhammad Jahangir Hossen Woo Seok Yang Yong Kim Jun Ho Kim Sungjae Yang Jeong-Hwan Kim Yung Hyup Joo Chang Seok Lee Joonho Choi Hong-Ju Shin Sungyoul Hong Song Seok Shin Jae Youl Cho NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton Mediators of Inflammation |
| title | NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton |
| title_full | NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton |
| title_fullStr | NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton |
| title_full_unstemmed | NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton |
| title_short | NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton |
| title_sort | nf κb ap 1 targeted inhibition of macrophage mediated inflammatory responses by depigmenting compound ap736 derived from natural 1 3 diphenylpropane skeleton |
| url | http://dx.doi.org/10.1155/2014/354843 |
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