Interleukin-33 affects cytokine production by keratinocytes in vitiligo
Summary Background Vitiligo is an acquired skin pigmentation disorder. Interleukin (IL)‐33 is a newly described member of the IL‐1 family. Aim To examine the role of IL‐33 and its regulation in vitiligo. Methods Expression of IL‐33 and its receptor (interleukin 1 receptor‐like 1 protein; also known...
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| Published in | Clinical and experimental dermatology Vol. 40; no. 2; pp. 163 - 170 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Blackwell Publishing Ltd
01.03.2015
Oxford University Press |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0307-6938 1365-2230 1365-2230 |
| DOI | 10.1111/ced.12464 |
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| Summary: | Summary
Background
Vitiligo is an acquired skin pigmentation disorder. Interleukin (IL)‐33 is a newly described member of the IL‐1 family.
Aim
To examine the role of IL‐33 and its regulation in vitiligo.
Methods
Expression of IL‐33 and its receptor (interleukin 1 receptor‐like 1 protein; also known as ST2), in skin biopsies taken from healthy subjects and patients with vitiligo, was examined by immunofluorescence staining and western blotting. IL‐33 secretion from primary keratinocytes was measured by ELISA. IL‐33‐stimulated release of stem cell factor (SCF), basic fibroblast growth factor (bFGF), IL‐6 and tumour necrosis factor (TNF)‐α from primary keratinocytes was examined by ELISA.
Results
IL‐33 and ST2 expression was increased in lesional skin, and serum IL‐33 was raised in patients with vitiligo. IL‐33 expression moved from the nucleus to the cytoplasm of keratinocytes. IL‐33 reduced expression of both SCF and bFGF, but increased expression of both IL‐6 and TNF‐α expression in primary keratinocytes.
Conclusions
IL‐33 is secreted by keratinocytes and functions as an alarmin. It may induce melanocyte death by regulating cytokines in the cellular microenvironment. |
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| Bibliography: | National Natural Sciences Foundation of China - No. 81171504; No. 81202352 Figure S1 Vitiligo Disease Activity Score (VIDA) scores and Vitiligo Area Scoring Index (VASI) of the patients with vitiligo. For the VASI, the percentage of vitiligo involvement is calculated in terms of hand units. One hand unit (which encompasses the palm plus the volar surface of all digits) is approximately equivalent to 1% of the total body surface area. The degree of pigmentation is estimated to the nearest one of the following percentages: 100%: complete depigmentation, no pigment is present; 90%: specks of pigment present; 75%: depigmented area exceeds the pigmented area; 50%: pigmented and depigmented areas are equal; 25%: pigmented area exceeds depigmented area; and 10%: only specks of depigmentation present. The VASI for each body region is determined by the product of the area of vitiligo in hand units and the extent of depigmentation within each hand unit measured patch. Total body VASI = all body sites (in hand units) × residual depigmentation. The VIDA is measured on a six-point scale: +4, active in the past 6 weeks; +3, active in the past 3 months; +2, active in the past 6 months; +1, active in the past 1 year; 0 stable for at least 1 year; -1 stable for at least 1 year, and spontaneously repigmenting.Figure S2 Immunofluorescent detection of IL-33 in HaCaT cells. HaCaT cells were cultured in the presence of tumour necrosis factor (TNF)-α for 24 h before cell permeation with PBS containing 0.2% Triton X-100 for 10 min. Cells were blocked with 5 mg/mL bovine serum albumin for 2 h. Cells were incubated with a primary anti-IL-33 antibody and Alexa Fluor 488-conjugated goat anti-rabbit IgG (H+L) antibody supplemented with Hoechst dye 33342 (1 μg/mL). Slides were viewed using a confocal laser scanning microscope (Leica SP5II) with a× 60 (NA = 1.40) oil objective lens, and images were acquired using Leica Las AF Lite software.Figure S3 Immunofluorescent detection of interleukin (IL)-33 and glial fibrillary acidic protein (GFAP) in human brain sections. Frozen sections of human brain, 10 μm thick, were stained with primary (mouse anti-human GFAP and rabbit anti-human IL-33) and secondary antibodies (Alexa Fluor 649-conjugated goat anti-mouse IgG and Alexa Fluor 488-conjugated donkey anti-rabbit IgG) and nuclei were visualized using Hoechst dye 33342 (1 μg/mL). Slides were viewed using a confocal laser scanning microscope as described above. Major State Basic Research Development Program of China - No. 2013CB530505 ArticleID:CED12464 ark:/67375/WNG-ZBHSSM3X-C istex:B325744F0A10237BCAD09567E13BE3B11F1E8B4B ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ISSN: | 0307-6938 1365-2230 1365-2230 |
| DOI: | 10.1111/ced.12464 |