{"title":"Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway","authors":"Zheng-Yi Li, Shu-Hao Chang, Kuang-Ting Liu, Alaina Edelie Wu, Chien-Sheng Hsu, Shi-Wei Huang, Mu-Chi Chung, Shih-Chung Wang, Jun-Kai Kao, Yi-Ju Chen, Jeng-Jer Shieh","doi":"10.1016/j.jdermsci.2023.12.005","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2023.12.005","url":null,"abstract":"<h3>Background</h3><p>Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity.</p><h3>Objective</h3><p>To explore whether IMQ could induce melanogenesis in melanoma cells.</p><h3>Methods</h3><p>The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not.</p><h3>Results</h3><p>We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity.</p><h3>Conclusions</h3><p>Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.</p>","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"62 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139031360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhixing Jiang, Chen Chen, Sen Yang, Hang He, Xiaoxia Zhu, Minrui Liang
{"title":"Contribution to the peripheral vasculopathy and endothelial cell dysfunction by CXCL4 in Systemic Sclerosis.","authors":"Zhixing Jiang, Chen Chen, Sen Yang, Hang He, Xiaoxia Zhu, Minrui Liang","doi":"10.21203/rs.3.rs-41064/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-41064/v1","url":null,"abstract":"BACKGROUND\u0000CXCL4, a chemokine with anti-angiogenic property, is involved in systemic sclerosis (SSc) related pulmonary arterial hypertension (PAH).\u0000\u0000\u0000OBJECTIVE\u0000To investigated the contribution of CXCL4 to SSc development by focusing on the correlation of circulatory CXCL4 levels with their peripheral vasculopathy, and the effect of CXCL4 on endothelial cell dysfunction and the potential signaling.\u0000\u0000\u0000METHODS\u0000We measured the plasma CXCL4 levels in 58 patients with SSc, 10 patients with the very early diagnosis of SSc (VEDOSS), and 80 healthy controls (HCs). Then, CXCL4 concentrations were correlated with clinical features, especially the peripheral vasculopathy. These observations were further validated in an additional cohort. Moreover, we studied the anti-angiogenic effects of CXCL4 and the underlying downstream signaling in human umbilical vein endothelial cells (HUVECs) in vitro.\u0000\u0000\u0000RESULTS\u0000Circulating CXCL4 levels were 103.62 % higher in patients with SSc and 201.51 % higher in patients with VEDOSS than matched HCs, which were confirmed in two independent cohorts. CXCL4 levels were associated with digital ulcers (DU) and nailfold videocapillaroscopy (NVC) abnormalities in SSc. The proliferation, migration, and tube formation of HUVECs were inhibited by CXCL4 or SSc derived plasma, which reversed by CXCL4 neutralizing antibody, but failed by CXCR3 inhibitor. CXCL4 downregulated the transcription factor Friend leukaemia integration factor-1 (Fli-1) via c-Abl signaling. Furthermore, CXCL4 blocked the transforming growth factor (TGF) -β or platelet-derived growth factor (PDGF) induced cell proliferation of HUVECs.\u0000\u0000\u0000CONCLUSIONS\u0000CXCL4 may contribute to peripheral vasculopathy in SSc by downregulating Fli-1 via c-Abl signaling in endothelial cells and interfering angiogenesis.","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"1 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2020-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85463837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matías Perrone Sibilia, María de Los Angeles Aldirico, A. Soto, M. S. Picchio, Vanesa R. Sánchez, Nadia Arcon, R. Moretta, V. Martín, S. Vanzulli, I. Fenoy, A. Goldman
{"title":"Chronic infection with the protozoan Toxoplasma gondii prevents the development of experimental atopic dermatitis in mice.","authors":"Matías Perrone Sibilia, María de Los Angeles Aldirico, A. Soto, M. S. Picchio, Vanesa R. Sánchez, Nadia Arcon, R. Moretta, V. Martín, S. Vanzulli, I. Fenoy, A. Goldman","doi":"10.1016/j.jdermsci.2019.10.007","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2019.10.007","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"9 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2019-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73198277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Nakajima, T. Miyagaki, H. Kamijo, T. Oka, Naomi Shishido-Takahashi, H. Suga, M. Sugaya, S. Sato
{"title":"Possible therapeutic applicability of galectin-9 in cutaneous T-cell lymphoma.","authors":"R. Nakajima, T. Miyagaki, H. Kamijo, T. Oka, Naomi Shishido-Takahashi, H. Suga, M. Sugaya, S. Sato","doi":"10.1016/j.jdermsci.2019.09.004","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2019.09.004","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"113 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2019-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80574037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Strober, A. Alikhan, B. Lockshin, Rebecca Shi, J. Cirulli, P. Schafer
{"title":"Apremilast mechanism of efficacy in systemic-naive patients with moderate plaque psoriasis: Pharmacodynamic results from the UNVEIL study.","authors":"B. Strober, A. Alikhan, B. Lockshin, Rebecca Shi, J. Cirulli, P. Schafer","doi":"10.1016/j.jdermsci.2019.09.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2019.09.003","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"69 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77360070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Meeting Report: Japan – Singapore International Skin Conference, Singapore April 10-12, 2019","authors":"","doi":"10.1016/j.jdermsci.2019.05.006","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2019.05.006","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"255 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73302344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Obituary: Stephen I. Katz, MD, PhD (1941–2018)","authors":"M. Amagai","doi":"10.1016/s0923-1811(19)30057-x","DOIUrl":"https://doi.org/10.1016/s0923-1811(19)30057-x","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"48 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74537209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Disrupted constitution of stratum corneum intercellular lipids contribute to barrier disruption in glycated epidermis","authors":"M. Yokota, H. Masaki, Y. Tokudome","doi":"10.1016/J.JDERMSCI.2017.02.134","DOIUrl":"https://doi.org/10.1016/J.JDERMSCI.2017.02.134","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"64 1","pages":"189"},"PeriodicalIF":4.6,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74414171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IL-10 producing plasma blasts that increase at an acute phase of herpes zoster","authors":"K. Fukuchi, K. Tatsuno, T. Shimauchi, Y. Tokura","doi":"10.1016/J.JDERMSCI.2017.02.197","DOIUrl":"https://doi.org/10.1016/J.JDERMSCI.2017.02.197","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"67 1","pages":"205"},"PeriodicalIF":4.6,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76531537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the role of Langerhans cells in primary cutaneous melanoma","authors":"J. Seidel, A. Otsuka, K. Kabashima","doi":"10.1016/J.JDERMSCI.2017.02.214","DOIUrl":"https://doi.org/10.1016/J.JDERMSCI.2017.02.214","url":null,"abstract":"","PeriodicalId":15641,"journal":{"name":"Journal of dermatological science","volume":"51 1","pages":"209"},"PeriodicalIF":4.6,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76253541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}