دورية أكاديمية
Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL-37, in a psoriasis mimicking microenvironment.
| العنوان: | Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL-37, in a psoriasis mimicking microenvironment. |
|---|---|
| المؤلفون: | Sigurgrimsdottir H; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.; Department of Immunology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland., Bjornsdottir EO; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.; Department of Immunology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland., Eysteinsdottir JH; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.; Department of Immunology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland., Olafsson JH; Faculty of Medicine, University of Iceland, Reykjavík, Iceland., Sigurgeirsson B; Faculty of Medicine, University of Iceland, Reykjavík, Iceland., Agnarsson BA; Department of Pathology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland., Einarsdottir HK; Department of Immunology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland., Freysdottir J; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.; Department of Immunology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland., Ludviksson BR; Faculty of Medicine, University of Iceland, Reykjavík, Iceland.; Department of Immunology, Landspitali-the National University Hospital of Iceland, Reykjavík, Iceland. |
| المصدر: | Scandinavian journal of immunology [Scand J Immunol] 2021 Dec; Vol. 94 (6), pp. e13096. Date of Electronic Publication: 2021 Oct 06. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0323767 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-3083 (Electronic) Linking ISSN: 03009475 NLM ISO Abbreviation: Scand J Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Blackwell Scientific Publications Original Publication: Oslo, Universitetsforlaget. |
| مواضيع طبية MeSH: | Psoriasis* , Vascular Endothelial Growth Factor A*/metabolism, Biomarkers/metabolism ; Chemokines/metabolism ; Humans ; Keratinocytes/metabolism ; Skin/pathology |
| مستخلص: | Psoriasis is an autoimmune disease driven by a Th17 response linked to the antimicrobial peptide (AMP) LL-37 that has been connected to the induction and chronicity of psoriasis. We show that keratinocytes secrete various immune biomarkers with a direct link to psoriasis immunopathogenesis. Under pro-inflammatory microenvironmental conditions, LL-37 was found to regulate keratinocyte secretion of various immune biomarkers (eg C-X-C motif chemokine ligand (CXCL)8 and interleukin (IL)-1β) and alter extracellular signal-regulated kinase (ERK)1/2 signalling. However, during neutral conditions LL-37 induced a different pattern of keratinocyte immune biomarker secretion (eg vascular endothelial growth factor, CXCL8 and IL-6). Thus, an interesting pattern emerged regarding the immunomodulatory effects of LL-37 on keratinocytes; in general, expression of immune biomarkers that were upregulated in a Th1-like microenvironment was downregulated in the presence of LL-37. In contrast, LL-37 reinforced the Th17 response. In active psoriatic skin lesions, LL-37 expression was found to be significantly upregulated, which was also evident from the unique diffuse epidermic expression pattern not found in healthy skin. Finally, successful phototherapy of psoriasis patients converted this LL-37 inflammatory psoriatic skin pattern into a more localized basal layer expression as found in healthy controls. Thus, these findings demonstrate that LL-37 has a significant role in skin immune homeostasis and that its interplay with keratinocytes may have a more direct role in the immunopathogenesis of psoriasis than previously thought. (© 2021 The Scandinavian Foundation for Immunology.) |
| References: | Lowes MA, Kikuchi T, Fuentes‐Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128:1207‐1211. Chiricozzi A, Guttman‐Yassky E, Suárez‐Fariñas M, et al. Integrative responses to IL‐17 and TNF‐alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011;131:677‐687. Sahmatova L, Sügis E, Šunina M, et al. Signs of innate immune activation and premature immunosenescence in psoriasis patients. Sci Rep. 2017;7:7553. Bruggen MC, Bauer WM, Reininger B, et al. In situ mapping of innate lymphoid cells in human skin: evidence for remarkable differences between normal and inflamed skin. J Invest Dermatol. 2016;136:2396‐2405. Johansen C, Rittig AH, Mose M, et al. STAT2 is involved in the pathogenesis of psoriasis by promoting CXCL11 and CCL5 production by keratinocytes. PLoS One. 2017;12:e0176994. Johnston A, Fritz Y, Dawes SM, et al. Keratinocyte overexpression of IL‐17C promotes psoriasiform skin inflammation. J Immunol. (2013);190, 2252‐2262. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi‐Joannopoulos K, Collins M, Fouser LA. Interleukin (IL)‐22 and IL‐17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006;203:2271‐2279. Braff MH, Di Nardo A, Gallo RL. Keratinocytes store the antimicrobial peptide cathelicidin in lamellar bodies. J Invest Dermatol. 2005;124:394‐400. Bai F, Zheng W, Dong Y, et al. Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta‐analysis. Oncotarget. 2018;9:1266‐1278. Takahashi H, Tsuji H, Hashimoto Y, Ishida‐Yamamoto A, Iizuka H. Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol. 2010;35:645‐649. Swindell WR, Sarkar MK, Liang Y, Xing X, Gudjonsson JE. Cross‐disease transcriptomics: unique IL‐17A signaling in psoriasis lesions and an autoimmune PBMC signature. J Invest Dermatol. 2016;136:1820‐1830. Kryczek I, Bruce AT, Gudjonsson JE, et al. Induction of IL‐17+ T cell trafficking and development by IFN‐gamma: mechanism and pathological relevance in psoriasis. J Immunol. 2008;181, 4733‐4741. Zhang L, Yang XQ, Cheng J, Hui RS, Gao TW. Increased Th17 cells are accompanied by FoxP3(+) Treg cell accumulation and correlated with psoriasis disease severity. Clini Immunol. 2010;135:108‐117. Frieder J, Kivelevitch D, Menter A. Secukinumab: a review of the anti‐IL‐17A biologic for the treatment of psoriasis. Ther Adv Chronic Dis. 2018;9:5‐21. Kennedy‐Crispin M, Billick E, Mitsui H, et al. Human keratinocytes' response to injury upregulates CCL20 and other genes linking innate and adaptive immunity. J Invest Dermatol. 2012;132:105‐113. Kanda N, Shimizu T, Tada Y, Watanabe S. IL‐18 enhances IFN‐gamma‐induced production of CXCL9, CXCL10, and CXCL11 in human keratinocytes. Eur J Immunol. 2007;37:338‐350. Lowes MA, Russell CB, Martin DA, Towne JE, Krueger JG. The IL‐23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013;34:174‐181. Lande R, Chamilos G, Ganguly D, et al. Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self‐DNA. Eur J Immunol. 2015;45:203‐213. Lande R, Botti E, Jandus C, et al. The antimicrobial peptide LL37 is a T‐cell autoantigen in psoriasis. Nat Commun. 2014;5:5621. Chen X, et al. Human antimicrobial peptide LL‐37 modulates proinflammatory responses induced by cytokine milieus and double‐stranded RNA in human keratinocytes. Biochem Biophys Res Comm. 2013;433:532‐537. Rodriguez‐Martinez S, Cancino‐Diaz JC, Vargas‐Zuniga LM, Cancino‐Diaz ME. LL‐37 regulates the overexpression of vascular endothelial growth factor (VEGF) and c‐IAP‐2 in human keratinocytes. Int J Dermatol. 2008;47:457‐462. Krutzik PO, Trejo A, Schulz KR, Nolan GP. Phospho flow cytometry methods for the analysis of kinase signaling in cell lines and primary human blood samples. Methods Mol Biol. 2011;699:179‐202. Fredriksson T, Pettersson U. Severe psoriasis–oral therapy with a new retinoid. Dermatologica. 1978;157:238‐244. Eysteinsdottir JH, Olafsson JH, Agnarsson BA, Luethviksson BR, Sigurgeirsson B. Psoriasis treatment: faster and long‐standing results after bathing in geothermal seawater. a randomized trial of three UVB phototherapy regimens. Photodermatol Photoimmunol Photomed. 2014;30:25‐34. Trozak DJ. Histologic grading system for psoriasis vulgaris. Int J Dermatol. 1994;33:380‐381. Babicki S, Arndt D, Marcu A, Liang Y, et al. Heatmapper: web‐enabled heat mapping for all. Nucleic Acids Res. 2016;44:W147‐W153. Scheller J, Chalaris A, Schmidt‐Arras D, Rose‐John S. The pro‐ and anti‐inflammatory properties of the cytokine interleukin‐6. Biochem Biophys Acta. 2011;1813:878‐888. Morizane S, Yamasaki K, Mühleisen B, et al. Cathelicidin antimicrobial peptide LL‐37 in psoriasis enables keratinocyte reactivity against TLR9 ligands. J Invest Dermatol. 2012;132:135‐143. Frohm M, Agerberth B, Ahangari G, et al. The expression of the gene coding for the antibacterial peptide LL‐37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem. 1997;272:15258‐15263. Wang S, Zhang Z, Peng H, Zeng K. Recent advances on the roles of epidermal growth factor receptor in psoriasis. Am J Transl Res. 2019;11:520‐528. Dumesic PA, Scholl FA, Barragan DI, Khavari PA. Erk1/2 MAP kinases are required for epidermal G2/M progression. J Cell Biol. 2009;185:409‐422. Wu Y, Liu L, Bian C, et al. MicroRNA let‐7b inhibits keratinocyte differentiation by targeting IL‐6 mediated ERK signaling in psoriasis. Cell Commun Signal. 2018;16:58. Xiong H, Xu Y, Tan G, Han Y, Tang Z, et al. Glycyrrhizin Ameliorates Imiquimod‐Induced Psoriasis‐like Skin Lesions in BALB/c Mice and Inhibits TNF‐a‐Induced ICAM‐1 Expression via NF‐κB/MAPK in HaCaT Cells. Cell Physiol Biochem. 2015;35(4):1335‐1346. http://dx.doi.org/10.1159/000373955. Cho JW, Lee KS, Kim CW. Curcumin attenuates the expression of IL‐1beta, IL‐6, and TNF‐alpha as well as cyclin E in TNF‐alpha‐treated HaCaT cells; NF‐kappaB and MAPKs as potential upstream targets. Int J Mol Med. 2007;19:469‐474. |
| معلومات مُعتمدة: | Icelandic Research Fund; Landspitali University Hospital Research Fund |
| فهرسة مساهمة: | Keywords: keratinocytes; psoriasis and antimicrobial peptides |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Chemokines) 0 (Vascular Endothelial Growth Factor A) |
| تواريخ الأحداث: | Date Created: 20220725 Date Completed: 20220726 Latest Revision: 20220726 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1111/sji.13096 |
| PMID: | 35872634 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1365-3083 |
|---|---|
| DOI: | 10.1111/sji.13096 |