Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation
Psoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/3523642 |
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| author | Chih-Hao Lu Chao-Yang Lai Da-Wei Yeh Yi-Ling Liu Yu-Wen Su Li-Chung Hsu Chung-Hsing Chang S.-L. Catherine Jin Tsung-Hsien Chuang |
| author_facet | Chih-Hao Lu Chao-Yang Lai Da-Wei Yeh Yi-Ling Liu Yu-Wen Su Li-Chung Hsu Chung-Hsing Chang S.-L. Catherine Jin Tsung-Hsien Chuang |
| author_sort | Chih-Hao Lu |
| collection | DOAJ |
| description | Psoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7–9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7–9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7–9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7–9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs. |
| format | Article |
| id | doaj-art-6ba297eb185e4a30a6892dcf5f40f98e |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-6ba297eb185e4a30a6892dcf5f40f98e2025-08-20T03:33:46ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/35236423523642Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic InflammationChih-Hao Lu0Chao-Yang Lai1Da-Wei Yeh2Yi-Ling Liu3Yu-Wen Su4Li-Chung Hsu5Chung-Hsing Chang6S.-L. Catherine Jin7Tsung-Hsien Chuang8Immunology Research Center, National Health Research Institutes, Miaoli, TaiwanImmunology Research Center, National Health Research Institutes, Miaoli, TaiwanImmunology Research Center, National Health Research Institutes, Miaoli, TaiwanImmunology Research Center, National Health Research Institutes, Miaoli, TaiwanImmunology Research Center, National Health Research Institutes, Miaoli, TaiwanInstitute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, TaiwanSkin Institute, Hualien Tzu Chi Hospital, Hualien, TaiwanDepartment of Life Sciences, National Central University, Zhongli District, Taoyuan, TaiwanImmunology Research Center, National Health Research Institutes, Miaoli, TaiwanPsoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7–9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7–9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7–9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7–9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs.http://dx.doi.org/10.1155/2018/3523642 |
| spellingShingle | Chih-Hao Lu Chao-Yang Lai Da-Wei Yeh Yi-Ling Liu Yu-Wen Su Li-Chung Hsu Chung-Hsing Chang S.-L. Catherine Jin Tsung-Hsien Chuang Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation Mediators of Inflammation |
| title | Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation |
| title_full | Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation |
| title_fullStr | Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation |
| title_full_unstemmed | Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation |
| title_short | Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation |
| title_sort | involvement of m1 macrophage polarization in endosomal toll like receptors activated psoriatic inflammation |
| url | http://dx.doi.org/10.1155/2018/3523642 |
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