Panhong Wu, Yonghui Liu, Hanxue Zhai, Xiaohan Wu, Aimin Liu
{"title":"芦丁通过调节 JAK2/STAT3 信号传导缓解角质形成细胞中与牛皮癣相关的炎症。","authors":"Panhong Wu, Yonghui Liu, Hanxue Zhai, Xiaohan Wu, Aimin Liu","doi":"10.1111/srt.70011","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease that can cause systemic inflammation in various organs. Rutin has been suggested to fight psoriasis, but the signaling pathways by which it works need to be explored.</p><p><strong>Materials and methods: </strong>HaCaT cells co-stimulated with interleukin (IL)-17, IL-22, tumor necrosis factor-alpha (TNF-α), IL-1α, and oncostatin M (M5) were used as an in vitro cell model of psoriasis. The proliferation and viability of HaCaT cells were determined by 5-ethynyl-2'-deoxyuridine and cell counting assays. Relative mRNA levels of IL-6, TNF-α, chemokines (CXCL1 and CXCL2), and anti-microbial peptides (S100A7 and S100A8) were detected by reverse transcriptase-quantitative PCR. Release of IL-6 and TNF-α from HaCaT cells was measured by enzyme-linked immunosorbent assay. Keratin1, Keratin5, p-JAK2, and p-STAT3 protein levels were estimated with western blotting. Molecular docking predicted binding sites for Rutin and STAT3.</p><p><strong>Results: </strong>Rutin treatment undercut M5-urged viability increase and proliferation boost in HaCaT cells. Moreover, M5 stimulation mediated upregulation of IL-6, TNF-α, CXCL1, CXCL2, S100A7, and S100A8 was partially reversed after Rutin treatment. In addition, M5 stimulation induced downregulation of Keratin1 and Keratin5 proteins as well as upregulation of p-JAK2 and p-STAT3 proteins were attenuated in response to Rutin treatment, manifesting that Rutin treatment inhibited M5-promoted aberrant differentiation and impaired M5-mediated activation of the JAK2/STAT3 signaling in HaCaT cells. Molecular docking discovered that residues GLN326 and ASP334 in STAT3 might bind to Rutin.</p><p><strong>Conclusion: </strong>Rutin treatment blocked the JAK2/STAT3 signaling, thus attenuating psoriasis-related inflammation and anomalous differentiation in keratinocytes.</p>","PeriodicalId":21746,"journal":{"name":"Skin Research and Technology","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337924/pdf/","citationCount":"0","resultStr":"{\"title\":\"Rutin alleviates psoriasis-related inflammation in keratinocytes by regulating the JAK2/STAT3 signaling.\",\"authors\":\"Panhong Wu, Yonghui Liu, Hanxue Zhai, Xiaohan Wu, Aimin Liu\",\"doi\":\"10.1111/srt.70011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disease that can cause systemic inflammation in various organs. Rutin has been suggested to fight psoriasis, but the signaling pathways by which it works need to be explored.</p><p><strong>Materials and methods: </strong>HaCaT cells co-stimulated with interleukin (IL)-17, IL-22, tumor necrosis factor-alpha (TNF-α), IL-1α, and oncostatin M (M5) were used as an in vitro cell model of psoriasis. The proliferation and viability of HaCaT cells were determined by 5-ethynyl-2'-deoxyuridine and cell counting assays. Relative mRNA levels of IL-6, TNF-α, chemokines (CXCL1 and CXCL2), and anti-microbial peptides (S100A7 and S100A8) were detected by reverse transcriptase-quantitative PCR. Release of IL-6 and TNF-α from HaCaT cells was measured by enzyme-linked immunosorbent assay. Keratin1, Keratin5, p-JAK2, and p-STAT3 protein levels were estimated with western blotting. Molecular docking predicted binding sites for Rutin and STAT3.</p><p><strong>Results: </strong>Rutin treatment undercut M5-urged viability increase and proliferation boost in HaCaT cells. Moreover, M5 stimulation mediated upregulation of IL-6, TNF-α, CXCL1, CXCL2, S100A7, and S100A8 was partially reversed after Rutin treatment. In addition, M5 stimulation induced downregulation of Keratin1 and Keratin5 proteins as well as upregulation of p-JAK2 and p-STAT3 proteins were attenuated in response to Rutin treatment, manifesting that Rutin treatment inhibited M5-promoted aberrant differentiation and impaired M5-mediated activation of the JAK2/STAT3 signaling in HaCaT cells. Molecular docking discovered that residues GLN326 and ASP334 in STAT3 might bind to Rutin.</p><p><strong>Conclusion: </strong>Rutin treatment blocked the JAK2/STAT3 signaling, thus attenuating psoriasis-related inflammation and anomalous differentiation in keratinocytes.</p>\",\"PeriodicalId\":21746,\"journal\":{\"name\":\"Skin Research and Technology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337924/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Skin Research and Technology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/srt.70011\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Skin Research and Technology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/srt.70011","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Rutin alleviates psoriasis-related inflammation in keratinocytes by regulating the JAK2/STAT3 signaling.
Background: Psoriasis is a chronic inflammatory skin disease that can cause systemic inflammation in various organs. Rutin has been suggested to fight psoriasis, but the signaling pathways by which it works need to be explored.
Materials and methods: HaCaT cells co-stimulated with interleukin (IL)-17, IL-22, tumor necrosis factor-alpha (TNF-α), IL-1α, and oncostatin M (M5) were used as an in vitro cell model of psoriasis. The proliferation and viability of HaCaT cells were determined by 5-ethynyl-2'-deoxyuridine and cell counting assays. Relative mRNA levels of IL-6, TNF-α, chemokines (CXCL1 and CXCL2), and anti-microbial peptides (S100A7 and S100A8) were detected by reverse transcriptase-quantitative PCR. Release of IL-6 and TNF-α from HaCaT cells was measured by enzyme-linked immunosorbent assay. Keratin1, Keratin5, p-JAK2, and p-STAT3 protein levels were estimated with western blotting. Molecular docking predicted binding sites for Rutin and STAT3.
Results: Rutin treatment undercut M5-urged viability increase and proliferation boost in HaCaT cells. Moreover, M5 stimulation mediated upregulation of IL-6, TNF-α, CXCL1, CXCL2, S100A7, and S100A8 was partially reversed after Rutin treatment. In addition, M5 stimulation induced downregulation of Keratin1 and Keratin5 proteins as well as upregulation of p-JAK2 and p-STAT3 proteins were attenuated in response to Rutin treatment, manifesting that Rutin treatment inhibited M5-promoted aberrant differentiation and impaired M5-mediated activation of the JAK2/STAT3 signaling in HaCaT cells. Molecular docking discovered that residues GLN326 and ASP334 in STAT3 might bind to Rutin.
Conclusion: Rutin treatment blocked the JAK2/STAT3 signaling, thus attenuating psoriasis-related inflammation and anomalous differentiation in keratinocytes.
期刊介绍:
Skin Research and Technology is a clinically-oriented journal on biophysical methods and imaging techniques and how they are used in dermatology, cosmetology and plastic surgery for noninvasive quantification of skin structure and functions. Papers are invited on the development and validation of methods and their application in the characterization of diseased, abnormal and normal skin.
Topics include blood flow, colorimetry, thermography, evaporimetry, epidermal humidity, desquamation, profilometry, skin mechanics, epiluminiscence microscopy, high-frequency ultrasonography, confocal microscopy, digital imaging, image analysis and computerized evaluation and magnetic resonance. Noninvasive biochemical methods (such as lipids, keratin and tissue water) and the instrumental evaluation of cytological and histological samples are also covered.
The journal has a wide scope and aims to link scientists, clinical researchers and technicians through original articles, communications, editorials and commentaries, letters, reviews, announcements and news. Contributions should be clear, experimentally sound and novel.