Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis
Abstract Psoriasis is a chronic inflammatory skin disease that affects 2–3% of the global population, and there is still no known possibility of a cure. Lipoxin A4 (LXA4), an endogenous lipoxygenase-derived eicosanoid mediator, has potent dual pro-resolving and anti-inflammatory properties. BML-111...
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Nature Portfolio
2017
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oai:doaj.org-article:6def1d129db54deaa68cb02207cc75b02021-12-02T16:06:55ZLipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis10.1038/s41598-017-07485-12045-2322https://doaj.org/article/6def1d129db54deaa68cb02207cc75b02017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07485-1https://doaj.org/toc/2045-2322Abstract Psoriasis is a chronic inflammatory skin disease that affects 2–3% of the global population, and there is still no known possibility of a cure. Lipoxin A4 (LXA4), an endogenous lipoxygenase-derived eicosanoid mediator, has potent dual pro-resolving and anti-inflammatory properties. BML-111 (5(S)-6(R)-7-trihydroxyheptanoic acid methyl ester), a lipoxin receptor agonist, has been previously confirmed to be equivalent to LXA4 in the anti-inflammatory processes. High mobility group box 1 (HMGB1) serves as an inflammatory cytokine when secreted extracellularly in psoriatic lesions and is involved in the development of psoriasis. Therefore, we investigated the effects of LXA4 and BML-111 on the HMGB1 signaling cascade and inflammation in lipopolysaccharide (LPS)-induced keratinocytes and imiquimod (IMQ)-induced psoriasiform dermatitis in mice. In the present study, we found that treatment with BML-111 attenuated the development of IMQ-induced psoriasiform dermatitis. Furthermore, treatment with BML-111 and LXA4 inhibited HMGB1 translocation from the nucleus to cytoplasm and downregulated the expression of toll-like receptor 4 (TLR4), receptor for advanced glycation end products (RAGE), p-ERK1/2, nuclear NF-κB p65, and proinflammatory cytokines in vivo and in vitro. Our findings indicate that LXA4 and its analog may be potential therapeutic candidates for psoriasis because of their ability to modulate the translocation and expression of HMGB1.Xinxin LiuXin WangXiaoru DuanDevesh PoorunJuntao XuSong ZhangLu GanMengwen HeKe ZhuZhangyin MingFeng HuHongxiang ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Xinxin Liu Xin Wang Xiaoru Duan Devesh Poorun Juntao Xu Song Zhang Lu Gan Mengwen He Ke Zhu Zhangyin Ming Feng Hu Hongxiang Chen Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis |
| description |
Abstract Psoriasis is a chronic inflammatory skin disease that affects 2–3% of the global population, and there is still no known possibility of a cure. Lipoxin A4 (LXA4), an endogenous lipoxygenase-derived eicosanoid mediator, has potent dual pro-resolving and anti-inflammatory properties. BML-111 (5(S)-6(R)-7-trihydroxyheptanoic acid methyl ester), a lipoxin receptor agonist, has been previously confirmed to be equivalent to LXA4 in the anti-inflammatory processes. High mobility group box 1 (HMGB1) serves as an inflammatory cytokine when secreted extracellularly in psoriatic lesions and is involved in the development of psoriasis. Therefore, we investigated the effects of LXA4 and BML-111 on the HMGB1 signaling cascade and inflammation in lipopolysaccharide (LPS)-induced keratinocytes and imiquimod (IMQ)-induced psoriasiform dermatitis in mice. In the present study, we found that treatment with BML-111 attenuated the development of IMQ-induced psoriasiform dermatitis. Furthermore, treatment with BML-111 and LXA4 inhibited HMGB1 translocation from the nucleus to cytoplasm and downregulated the expression of toll-like receptor 4 (TLR4), receptor for advanced glycation end products (RAGE), p-ERK1/2, nuclear NF-κB p65, and proinflammatory cytokines in vivo and in vitro. Our findings indicate that LXA4 and its analog may be potential therapeutic candidates for psoriasis because of their ability to modulate the translocation and expression of HMGB1. |
| format |
article |
| author |
Xinxin Liu Xin Wang Xiaoru Duan Devesh Poorun Juntao Xu Song Zhang Lu Gan Mengwen He Ke Zhu Zhangyin Ming Feng Hu Hongxiang Chen |
| author_facet |
Xinxin Liu Xin Wang Xiaoru Duan Devesh Poorun Juntao Xu Song Zhang Lu Gan Mengwen He Ke Zhu Zhangyin Ming Feng Hu Hongxiang Chen |
| author_sort |
Xinxin Liu |
| title |
Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis |
| title_short |
Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis |
| title_full |
Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis |
| title_fullStr |
Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis |
| title_full_unstemmed |
Lipoxin A4 and its analog suppress inflammation by modulating HMGB1 translocation and expression in psoriasis |
| title_sort |
lipoxin a4 and its analog suppress inflammation by modulating hmgb1 translocation and expression in psoriasis |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/6def1d129db54deaa68cb02207cc75b0 |
| work_keys_str_mv |
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| _version_ |
1718384781013549056 |