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本维莫德乳膏治疗特应性皮炎的研究进展
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Abstract:
特应性皮炎(AD)是一种慢性、复发性、炎症性、瘙痒性皮肤病。其发病机制复杂，目前认为与遗传、环境、皮肤屏障异常及免疫系统紊乱有关。皮肤屏障功能障碍与丝聚蛋白(FLG)、兜甲蛋白(LOR)、内披蛋白(IVL)等的下调有关。Th2型皮肤炎症是AD的基本特征，IL4和IL-13是AD发病的重要细胞因子。本维莫德乳膏作为芳香烃受体/核因子E2相关因子(AHR/NRF2)的双重激活剂对AD的多种致病机制具有调节作用，本文就目前本维莫德乳膏治疗AD的研究进展进行综述。
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory, pruritus skin disease. Its pathogenesis is complex, and it is currently believed to be related to heredity, environment, abnormal skin barrier and immune system disorder. Skin barrier dysfunction is associated with down regulation of Filaggrin (FLG), Loricrin (LOR), and Involucrin (IVL). Th2 skin inflammation is a basic feature of AD, and IL4 and IL-13 are important cytokines in AD pathogenesis. As a double activator of aryl hydrocarbon receptor/nuclear factor E2-related factor 2 (AHR/NRF2), Benvitimod cream has a regulatory effect on various pathogenic mechanisms of AD. This paper reviews the current research progress of Benvitimod in the treatment of atopic dermatitis.
| [1] | Gittler, J.K., Shemer, A., Suárez-Fari？as, M., et al. (2012) Progressive Activation of T(H)2/T(H)22 Cytokines and Selective Epidermal Proteins Characterizes Acute and Chronic Atopic Dermatitis. Journal of Allergy and Clinical Immunology, 130, 1344-1354. https://doi.org/10.1016/j.jaci.2012.07.012 |
| [2] | Koga, C., Kabashima, K., Shiraishi, N., et al. (2008) Possible Pathogenic Role of Th17 Cells for Atopic Dermatitis. Journal of Investigative Dermatology, 128, 2625-2630. https://doi.org/10.1038/jid.2008.111 |
| [3] | Furue, M., Iida, K., Imaji, M., et al. (2018) Microbiome Analysis of Forehead Skin in Patients with Atopic Dermatitis and Healthy Subjects: Implication of Staphylococcus and Corynebacterium. The Journal of Dermatology, 45, 877.
https://doi.org/10.1111/1346-8138.14486 |
| [4] | Iwamoto, K., Moriwaki, M., Miyake, R., et al. (2019) Staphylo-coccus aureus in Atopic Dermatitis: Strain-Specific Cell Wall Proteins and Skin Immunity. Allergology International, 68, 309-315. https://doi.org/10.1016/j.alit.2019.02.006 |
| [5] | Bissonnette, R., Poulin, Y., Zhou, Y., et al. (2012) Efficacy and Safety of Topical WBI-1001 in Patients with Mild to Severe Atopic Dermatitis: Results from a 12-Week, Multicentre, Randomized, Placebo-Controlled Double-Blind Trial. Br. The Journal of Dermatology, 166, 853-860. https://doi.org/10.1111/j.1365-2133.2011.10775.x |
| [6] | Keam, S.J. (2022) Tapinar of Cream 1%: First Approval. Drugs, 82, 1221-1228.
https://doi.org/10.1007/s40265-022-01748-6 |
| [7] | Li, J., Chen, G., Wu, H., et al. (1995) Identification of Two Pigments and a Hydroxystilbene Antibiotic from Photorhabdus luminescens. Applied and Environmental Microbiology, 61, 4329-4333.
https://doi.org/10.1128/aem.61.12.4329-4333.1995 |
| [8] | Richardson, W.H., Schmidt, T.M. and Nealson, K.H. (1988) Identification of an Anthraqui-None Pigment and a Hydroxystilbene Antibiotic from Xenorhabdus luminescens. Applied and Environmental Microbiology, 54, 1602-1605.
https://doi.org/10.1128/aem.54.6.1602-1605.1988 |
| [9] | Bissonnette, R., Chen, G., Bolduc, C., et al. (2010) Efficacy and Safety of Topical WBI-1001 in the Treatment of Atopic Dermatitis: Results from a Phase 2A, Randomized, Placebo-Controlled Clinical Trial. Archives of Dermatology, 146, 446-449. https://doi.org/10.1001/archdermatol.2010.34 |
| [10] | Smith, S.H., Jayawickreme, C., Rickard, D.J., et al. (2017) Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans. Journal of Investigative Dermatology, 137, 2110-2119.
https://doi.org/10.1016/j.jid.2017.05.004 |
| [11] | Tsuji, G., Takahara, M., Uchi, H., et al. (2012) Identification of Ketoconazole as an AhR-Nrf2 Activator in Cultured Human Keratinocytes: The Basis of Its Anti-Inflammatory Effect. Journal of Investigative Dermatology, 132, 59-68.
https://doi.org/10.1038/jid.2011.194 |
| [12] | Hwang, J., Newton, E.M., Hsiao, J., et al. (2022) Aryl Hydrocarbon Receptor/Nuclear Factor E2-Related Factor 2 (AHR/NRF2) Signalling: A Novel Therapeutic Target for Atopic Dermatitis. Experimental Dermatology, 31, 485-497.
https://doi.org/10.1111/exd.14541 |
| [13] | Mimura, J. and Fujii-Kuriyama, Y. (2003) Functional Role of AhR in the Expression of Toxic Effects by TCDD. Biochimica et Biophysica Acta, 1619, 263-268. https://doi.org/10.1016/S0304-4165(02)00485-3 |
| [14] | Hayes, J.D. and McMahon, M. (2001) Molecular Basis for the Contribution of the Antioxidant Responsive Element to Cancer Chemoprevention. Cancer Letters, 174, 103-113. https://doi.org/10.1016/S0304-3835(01)00695-4 |
| [15] | Miao, W., Hu, L., Scrivens, P.J., et al. (2005) Transcriptional Regulation of NF-E2 p45-Related Factor (NRF2) Expression by the Aryl Hydrocarbon Receptor-Xenobiotic Response Element Signaling Pathway: Direct Cross-Talk between Phase I and II Drug-Metabolizing Enzymes. Journal of Biological Chemistry, 280, 20340-20348.
https://doi.org/10.1074/jbc.M412081200 |
| [16] | Esser, C. and Rannug, A. (2015) The Aryl Hydrocarbon Receptor in Barrier Organ Physiology, Immunology, and Toxicology. Pharmacological Reviews, 67, 259-279. https://doi.org/10.1124/pr.114.009001 |
| [17] | Esser, C. (2016) The Aryl Hydrocarbon Receptor in Immunity: Tools and Potential. Methods in Molecular Biology, 1371, 239-257. https://doi.org/10.1007/978-1-4939-3139-2_16 |
| [18] | Stockinger, B., Di Meglio, P., Gialitakis, M., et al. (2014) The Aryl Hydrocarbon Receptor: Multitasking in the Immune System. Annual Review of Immunology, 32, 403-432. https://doi.org/10.1146/annurev-immunol-032713-120245 |
| [19] | Mischke, D., Korge, B.P., Marenholz, I., et al. (1996) Genes Encoding Structural Proteins of Epidermal Cornification and S100 Calcium-Binding Proteins form a Gene Complex (“Epidermal Differentiation Complex”) on Human Chromosome 1q21. Journal of Investigative Dermatology, 106, 989-992. https://doi.org/10.1111/1523-1747.ep12338501 |
| [20] | Sutter, C.H., Bodreddigari, S., Campion, C., et al. (2011) 2,3,7,8-Tetrachlorodibenzo-p-dioxin Increases the Expression of Genes in the Human Epidermal Differentiation Complex and Accelerates Epidermal Barrier Formation. Toxicological Sciences, 124, 128-137. https://doi.org/10.1093/toxsci/kfr205 |
| [21] | Stemmler, S., Nothnagel, M., Parwez, Q., et al. (2009) Variation in Genes of the Epidermal Differentiation Complex in German Atopic Dermatitis Patients. International Journal of Immunogenetics, 36, 217-222.
https://doi.org/10.1111/j.1744-313X.2009.00858.x |
| [22] | Allam, J.P., Bieber, T. and Novak, N. (2005) Recent Highlights in the Pathophysiology of Atopic Eczema. International Archives of Allergy and Immunology, 136, 191-197. https://doi.org/10.1159/000083893 |
| [23] | Guttman-Yassky, E., Krueger, J.G. and Lebwohl, M.G. (2017) Systemic Immune Mechanisms in Atopic Dermatitis and Psoriasis with Implications for Treatment. Experimental Dermatology, 27, 409-417.
https://doi.org/10.1111/exd.13336 |
| [24] | Mansouri, Y. and Guttman-Yassky, E. (2015) Immune Pathways in Atopic Dermatitis, and Definition of Biomarkers through Broad and Targeted Therapeutics. Journal of Clinical Medicine, 4, 858-873.
https://doi.org/10.3390/jcm4050858 |
| [25] | Arima, K., Gupta, S., Gadkari, A., et al. (2018) Burden of Atopic Der-matitis in Japanese Adults: Analysis of Data from the 2013 National Health and Wellness Survey. The Journal of Dermatology, 45, 390-396.
https://doi.org/10.1111/1346-8138.14218 |
| [26] | Igarashi, A., Fujita, H., Arima, K., Inoue, et al. (2019) Health-Care Resource Use and Current Treatment of Adult Atopic Dermatitis Patients in Japan: A Retrospective Claims Database Analysis. The Journal of Dermatology, 46, 652-661. https://doi.org/10.1111/1346-8138.14947 |
| [27] | Jung, H.J., Bae, J.Y., Kim, J.E., et al. (2018) Survey of Disease Awareness, Treatment Behavior and Treatment Satisfaction in Pa-tients with Atopic Dermatitis in Korea: A Multicenter Study. The Journal of Dermatology, 45, 1172-1180.
https://doi.org/10.1111/1346-8138.14540 |
| [28] | Komura, Y., Kogure, T., Kawahara, K., et al. (2018) Economic Assessment of Actual Prescription of Drugs for Treatment of Atopic Dermatitis: Differences between Dermatology and Pediatrics in Large-Scale Receipt Data. The Journal of Dermatology, 45, 165-174. https://doi.org/10.1111/1346-8138.14133 |
| [29] | Takeuchi, S., Oba, J., Esaki, H., et al. (2018) Non-Corticosteroid Adherence and Itch Severity Influence Perception of Itch in Atopic Dermatitis. The Journal of Dermatology, 45, 158-164. https://doi.org/10.1111/1346-8138.14124 |
| [30] | Williams, H., Stewart, A., von Mutius, E., et al. (2008) Is Eczema Really on the Increase Worldwide? Journal of Allergy and Clinical Immunology, 121, 947-954. https://doi.org/10.1016/j.jaci.2007.11.004 |
| [31] | Van den Bogaard, E.H., Bergboer, J.G., Vonk-Bergers, M., et al. (2013) Coal Tar Induces AHR-Dependent Skin Barrier Repair in Atopic Dermatitis. Journal of Clinical Investigation, 123, 917-927. https://doi.org/10.1172/JCI65642 |
| [32] | Geng, S., Mezentsev, A., Kalachikov, S., et al. (2006) Tar-geted Ablation of Arnt in Mouse Epidermis Results in Profound Defects in Desquamation and Epidermal Barrier Func-tion. Journal of Cell Science, 119, 4901-4912.
https://doi.org/10.1242/jcs.03282 |
| [33] | 王建琴. 中国特应性皮炎诊疗指南(2020版)解读[J]. 皮肤性病诊疗学杂志, 2020, 27(5): 359-361. |
| [34] | Czarnowicki, T., Gonzalez, J., Bonifacio, K.M., et al. (2016) Diverse Activation and Differentiation of Multiple B-Cell Subsets in Patients with Atopic Dermatitis but Not in Patients with Psoriasis. Journal of Allergy and Clinical Immunology, 137, 118-129.e115. https://doi.org/10.1016/j.jaci.2015.08.027 |
| [35] | Furue, M. (2020) Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis. International Journal of Molecular Sciences, 21, 5382.
https://doi.org/10.3390/ijms21155382 |
| [36] | Nomura, T., Sandilands, A., Akiyama, M., et al. (2007) Unique Muta-tions in the Filaggrin Gene in Japanese Patients with Ichthyosis Vulgaris and Atopic Dermatitis. Journal of Allergy and Clinical Immunology, 119, 434-440.
https://doi.org/10.1016/j.jaci.2006.12.646 |
| [37] | Palmer, C.N.A., Irvine, A.D., Terron-Kwiatkowski, A., et al. (2006) Common Loss-of-Function Variants of the Epidermal Barrier Protein Filaggrin Are a Major Predisposing Factor for Atopic Dermatitis. Nature Genetics, 38, 441-446.
https://doi.org/10.1038/ng1767 |
| [38] | Steinert, P.M. and Marekov, L.N. (1995) The Proteins Elafin, Filaggrin, Keratin Intermediate Filaments, Loricrin, and Small Proline-Rich Proteins 1 and 2 Are Isodipeptide Cross-Linked Components of the Human Epidermal Cornified Cell Envelope. Journal of Biological Chemistry, 270, 17702-17711. https://doi.org/10.1074/jbc.270.30.17702 |
| [39] | Hudson, T.J. (2006) Skin Barrier Function and Allergic Risk. Na-ture Genetics, 38, 399-400.
https://doi.org/10.1038/ng0406-399 |
| [40] | Candi, E., Melino, G., Mei, G., et al. (1995) Biochemical, Structural, and Transglutaminase Substrate Properties of Human Loricrin, the Major Epidermal Cornified Cell Envelope Protein. Journal of Biological Chemistry, 270, 26382- 26390. https://doi.org/10.1074/jbc.270.44.26382 |
| [41] | Robinson, N.A., Lapic, S., Welter, J.F., et al. (1997) S100A11, S100A10, Annexin I, Desmosomal Proteins, Small Proline-Rich Proteins, Plasminogen Activator Inhibitor-2, and Involucrin Are Components of the Cornified Envelope of Cultured Human Epidermal Keratinocytes. Journal of Biological Chemistry, 272, 12035-12046.
https://doi.org/10.1074/jbc.272.18.12035 |
| [42] | Yu, J., Luo, Y., Zhu, Z., et al. (2019) A Tryptophan Metabolite of the Skin Microbiota Attenuates Inflammation in Patients with Atopic Dermatitis through the Aryl Hydrocarbon Receptor. Journal of Allergy and Clinical Immunology, 143, 2108-2119.e2112. https://doi.org/10.1016/j.jaci.2018.11.036 |
| [43] | Buommino, E., Baroni, A., Papulino, C., et al. (2018) Malassezia Pachydermatis Upregulates AhR Related CYP1A1 Gene and Epidermal Barrier Markers in Human Keratinocytes. Medical Mycology, 56, 987-993.
https://doi.org/10.1093/mmy/myy004 |
| [44] | Furue, M. (2020) Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4-JAK- STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis. Journal of Clinical Medicine, 9, 3741. https://doi.org/10.3390/jcm9113741 |
| [45] | Kim, B.E., Leung, D.Y., Boguniewicz, M., et al. (2008) Loricrin and Involucrin Expression Is Down-Regulated by Th2 Cytokines through STAT-6. Clinical Immunology (Orlando, Fla), 126, 332-337.
https://doi.org/10.1016/j.clim.2007.11.006 |
| [46] | Bao, L., Mohan, G.C., Alexander, J.B., et al. (2017) A Molecular Mechanism for IL-4 Suppression of Loricrin Transcription in Epidermal Keratinocytes: Implication for Atopic Dermatitis Pathogenesis. Innate Immunity, 23, 641-647.
https://doi.org/10.1177/1753425917732823 |
| [47] | Howell, M.D., Kim, B.E., Gao, P., et al. (2007) Cytokine Mod-ulation of Atopic Dermatitis Filaggrin Skin Expression. Journal of Allergy and Clinical Immunology, 120, 150-155. https://doi.org/10.1016/j.jaci.2007.04.031 |
| [48] | Amano, W., Nakajima, S., Kunugi, H., et al. (2015) The Janus Kinase Inhibitor JTE-052 Improves Skin Barrier Function through Suppressing Signal Transducer and Activator of Transcription 3 Signaling. Journal of Allergy and Clinical Immunology, 136, 667-677.e667. https://doi.org/10.1016/j.jaci.2015.03.051 |
| [49] | Bao, L., Shi, V.Y. and Chan, L.S. (2012) IL-4 Regulates Chemo-kine CCL26 in Keratinocytes through the Jak 1,2/Stat6 Signal Transduction Pathway: Implication for Atopic Dermatitis. Molecular Immunology, 50, 91-97.
https://doi.org/10.1016/j.molimm.2011.12.008 |
| [50] | Bao, L., Shi, V.Y. and Chan, L.S. (2013) IL-4 Up-Regulates Epidermal Chemotactic, Angiogenic, and Pro-Inflam- matory Genes and Down-Regulates Antimicrobial Genes in Vivo and in Vitro: Relevant in the Pathogenesis of Atopic Dermatitis. Cytokine, 61, 419-425. https://doi.org/10.1016/j.cyto.2012.10.031 |
| [51] | Tsuji, G., Hashimoto-Hachiya, A., Kiyomatsu-Oda, M., et al. (2017) Aryl Hydrocarbon Receptor Activation Restores Filaggrin Expression via OVOL1 in Atopic Dermatitis. Cell Death & Disease, 8, e2931.
https://doi.org/10.1038/cddis.2017.322 |
| [52] | Takei, K., Mitoma, C., Hashimoto-Hachiya, A., et al. (2015) Antioxi-dant Soybean Tar Glyteer Rescues T-Helper-Media- ted Downregulation of Filaggrin Expression via Aryl Hydrocarbon Receptor. The Journal of Dermatology, 42, 171-180.
https://doi.org/10.1111/1346-8138.12717 |
| [53] | Miake, S., Tsuji, G., Takemura, M., et al. (2019) IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl17 and Ccl22 Production in Dendritic Cells: Implica-tions for Atopic Dermatitis. International Journal of Molecular Sciences, 20, 60. https://doi.org/10.3390/ijms20164053 |
| [54] | Veldhoe, M., Hirota, K., Westendorf, A.M., et al. (2008) The Aryl Hydrocarbon Receptor Links TH17-Cell-Mediated Autoimmunity to Environmental Toxins. Nature, 453, 106-109. https://doi.org/10.1038/nature06881 |
| [55] | Koch, S., Stroisch, T.J., Vorac, J., et al. (2017) AhR Mediates an Anti-inflammatory Feedback Mechanism in Human Langerhans Cells Involving FcεRI and IDO. Allergy, 72, 1686-1693. https://doi.org/10.1111/all.13170 |
| [56] | Yoo, O.K., Choi, W.J. and Keum, Y.S. (2020) Cardamonin Inhibits Oxazolone-Induced Atopic Dermatitis by the Induction of NRF2 and the Inhibition of Th2 Cytokine Production. Anti-oxidants (Basel Switzerland), 9, 834.
https://doi.org/10.3390/antiox9090834 |
| [57] | Hendricks, A.J., Eichenfield, L.F. and Shi, V.Y. (2020) The Impact of Airborne Pollution on Atopic Dermatitis: A Literature Review. British Journal of Dermatology, 183, 16-23. https://doi.org/10.1111/bjd.18781 |
| [58] | Peppers, J., Paller, A.S., Maeda-Chubachi, T., et al. (2019) A Phase 2, Randomized Dose-Finding Study of Tapinarof (GSK2894512 Cream) for the Treatment of Atopic Dermatitis. Journal of the American Academy of Dermatology, 80, 89-98.e3. https://doi.org/10.1016/j.jaad.2018.06.047 |
| [59] | Paller, A.S., Stein Gold, L., Soung, J., et al. (2021) Efficacy and Patient-Reported Outcomes from a Phase 2b, Randomized Clinical Trial of Tapinarof Cream for the Treatment of Adolescents and Adults with Atopic Dermatitis. Journal of the American Academy of Dermatology, 84, 632-638. https://doi.org/10.1016/j.jaad.2020.05.135 |
| [60] | Hamada, M., Furusyo, N., Urabe, K., et al. (2005) Prevalence of Atopic Dermatitis and Serum IgE Values in Nursery School Children in Ishigaki Island, Okinawa, Japan. The Journal of Dermatology, 32, 248-255.
https://doi.org/10.1111/j.1346-8138.2005.tb00757.x |
| [61] | Bissonnette, R., Vasist, L.S., Bullman, J.N., et al. (2018) Systemic Pharmacokinetics, Safety, and Preliminary Efficacy of Topical AhR Agonist Tapinarof: Results of a Phase 1 Study. Clinical Pharmacology in Drug Development, 7, 524-531.
https://doi.org/10.1002/cpdd.439 |
