Koebnerisin (S100A15): A novel player in the pathogenesis of rosacea

医学 酒渣鼻 发病机制 皮肤病科 病理 痤疮
作者
Aleksandra Batycka-Baran,E. Hattinger,Aleksander Marchenkov,Maria Kozioł,Andrzej Bieniek,Jacek C. Szepietowski,Thomas Ruzicka,Ronald Wolf
出处
期刊:Journal of The American Academy of Dermatology [Elsevier BV]
卷期号:80 (6): 1753-1755 被引量:10
标识
DOI:10.1016/j.jaad.2018.06.012
摘要

Rosacea is one of the most common chronic inflammatory skin diseases that mainly affects the white adult population. The pathophysiology of rosacea is still not completely elucidated. Growing evidence indicates that the aberrant innate immune response might play an essential role in this disease.1Gallo R.L. Granstein R.D. Kang S. et al.Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee.J Am Acad Dermatol. 2018; 78: 148-155Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar S100 proteins are a family of small (9-13 kDa), calcium-binding molecules involved in the regulation of cell signaling, metabolism, and proliferation. A member of the S100 protein family, koebnerisin (S100A15), is an innate, antimicrobial peptide with diverse proinflammatory functions encoded by a gene located within the epidermal differentiation complex on chromosome 1q21. The S100A15 gene is transcribed into 2 alternate mRNA splice variants, the short (S100A15-S) and long (S100A15-L) isoforms, that share the same coding region but are differentially regulated.2Wolf R. Ruzicka T. Yuspa S.H. Novel S100A7 (Psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function.Amino Acids. 2011; 41: 789-796Crossref PubMed Scopus (59) Google Scholar Koebnerisin has been shown to act as an alarmin or has a danger-associated molecular pattern (DAMP). In response to some endogenous or exogenous stimuli, koebnerisin enhances immune-mediated inflammatory processes in the skin.2Wolf R. Ruzicka T. Yuspa S.H. Novel S100A7 (Psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function.Amino Acids. 2011; 41: 789-796Crossref PubMed Scopus (59) Google Scholar, 3Wolf R. Howard O.M. Dong H.F. et al.Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.J Immunol. 2008; 181: 1499-1506Crossref PubMed Scopus (136) Google Scholar, 4Hegyi Z. Zwicker S. Bureik D. et al.Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced proinflammatory S100 “alarmins” Psoriasin (S100A7) and koebnerisin (S100A15) in psoriasis.J Invest Dermatol. 2012; 132: 1416-1424Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Koebnerisin was first found to be up-regulated in psoriatic skin lesions; however, it also appears to play an important role in other chronic inflammatory skin diseases, such as acne vulgaris.2Wolf R. Ruzicka T. Yuspa S.H. Novel S100A7 (Psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function.Amino Acids. 2011; 41: 789-796Crossref PubMed Scopus (59) Google Scholar, 5Borovaya A. Dombrowski Y. Zwicker S. et al.Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris.Arch Dermatol Res. 2014; 306: 689-700Google Scholar In inflamed skin, koebnerisin is expressed by various cells, such as keratinocytes, fibroblast, endothelial cells, and dendritic cells.2Wolf R. Ruzicka T. Yuspa S.H. Novel S100A7 (Psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function.Amino Acids. 2011; 41: 789-796Crossref PubMed Scopus (59) Google Scholar The role of koebnerisin in rosacea has not been investigated. The objective of the present study was to investigate the expression and function of koebnerisin in rosacea. The study group consisted of patients with moderate and severe rosacea (n = 6). Skin biopsies were taken from inflammatory, erythematopapular lesions located on the face. All patients were white, had skin of phototype I-III, and were 47-66 (mean ± standard deviation 56.83 ± 7.03) years of age. The control group was matched by race, sex, and age and consisted of healthy volunteers who underwent facial plastic surgery procedures (n = 6). The expression of koebnerisin in skin lesions of patients with rosacea and controls was assessed by quantitative reverse transcription PCR and immunofluorescent analysis. The regulation and function of koebnerisin in rosacea-relevant human skin cell cultures, keratinocytes, and fibroblasts were assessed by quantitative reverse transcription PCR. In the present study, we found that koebnerisin was upregulated in rosacea lesional skin compared with healthy skin (Fig 1). Koebnerisin was overexpressed in the epidermis by suprabasal and basal keratinocytes as well as in the dermis. The upregulation of koebnerisin in the epidermis suggests its potential role in the regulation of keratinocytes proliferation and function. Moreover, by being overexpressed in rosacea skin lesions, koebnerisin might exert a proinflammatory effect. A previously conducted study showed that koebnerisin acts as a chemoattractant for monocytes and neutrophils, which play a significant role in the pathogenesis of rosacea.3Wolf R. Howard O.M. Dong H.F. et al.Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15.J Immunol. 2008; 181: 1499-1506Crossref PubMed Scopus (136) Google Scholar Furthermore, it has been demonstrated that koebnerisin has the ability to prime keratinocytes and leukocytes for enhanced production of proinflammatory cytokines, eg, tumor necrosis factor α (TNF-α), interleukin (IL) 6, IL-8, and IL-1β.4Hegyi Z. Zwicker S. Bureik D. et al.Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced proinflammatory S100 “alarmins” Psoriasin (S100A7) and koebnerisin (S100A15) in psoriasis.J Invest Dermatol. 2012; 132: 1416-1424Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 6Batycka-Baran A. Hattinger E. Zwicker S. et al.Leukocyte-derived koebnerisin (S100A15) and Psoriasin (S100A7) are systemic mediators of inflammation in psoriasis.J Dermatol Sci. 2015; 79: 214-221Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Recent studies have indicated a significant role for TNF-α and IL-1β in rosacea.1Gallo R.L. Granstein R.D. Kang S. et al.Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee.J Am Acad Dermatol. 2018; 78: 148-155Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar We also demonstrated that TNF-α enhanced the expression of koebnerisin in keratinocytes and fibroblasts (Fig 2, A and B), which might create a vicious circular cycle of inflammation. In the present study, we also showed that koebnerisin might play an additional proangiogenic role stimulating keratinocytes and fibroblasts to enhance the production of the potent proangiogenic mediator vascular endothelial growth factor, and we further demonstrated that koebnerisin primed fibroblasts for increased expression of matrix metalloproteinase 9 (Fig 2, C-F). Matrix metalloproteinase 9 has a destructive effect on dermal components and, thus, stimulates the innate immune response and inflammatory processes.1Gallo R.L. Granstein R.D. Kang S. et al.Standard classification and pathophysiology of rosacea: the 2017 update by the National Rosacea Society Expert Committee.J Am Acad Dermatol. 2018; 78: 148-155Abstract Full Text Full Text PDF PubMed Scopus (224) Google ScholarFig 2Quantitative reverse transcription PCR of mRNA in healthy human skin and lesional skin from patients with moderate and severe rosacea. A and B, Koebnerisin (S100A15) enhances the expression of VEGF and does not influence the expression of MMP-9 in human keratinocytes. C and D, Koebnerisin enhances the expression of VEGF and MMP-9 in human fibroblasts. E, TNF-α and IL-17A enhances the expression of koebnerisin in human keratinocytes F, TNF-α enhances the expression of koebnerisin in human fibroblasts. Data represent mean ± standard error of mean. *P = .05. IL-17A, Interleukin 17A; MMP-9, matrix metalloproteinase-9; TNF-α, tumor necrosis factor α; VEGF, vascular endothelial growth factor.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In conclusion, koebnerisin (S100A15) might emerge as a novel player in the pathogenesis of rosacea. Balancing the activities of certain antimicrobial proteins might be a goal for future therapeutic interventions in rosacea.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
细心觅风完成签到,获得积分10
1秒前
铅笔995发布了新的文献求助20
1秒前
大个应助ryd采纳,获得10
1秒前
2秒前
Yi羿完成签到 ,获得积分10
3秒前
3秒前
5秒前
6秒前
xinlei2023完成签到,获得积分10
7秒前
耿大海发布了新的文献求助10
8秒前
yn发布了新的文献求助10
8秒前
长白发布了新的文献求助10
9秒前
今后应助铅笔995采纳,获得10
11秒前
cccong1210发布了新的文献求助30
11秒前
11秒前
学术小白完成签到,获得积分10
11秒前
Adam完成签到,获得积分10
12秒前
扁桃体不发言完成签到,获得积分10
12秒前
ye完成签到,获得积分10
13秒前
许起眸发布了新的文献求助10
14秒前
15秒前
17秒前
懒123完成签到,获得积分10
17秒前
可爱的函函应助一二一采纳,获得10
18秒前
萨特完成签到,获得积分10
18秒前
Ljy发布了新的文献求助10
19秒前
量子星尘发布了新的文献求助10
21秒前
21秒前
21秒前
希望天下0贩的0应助Elaine采纳,获得10
22秒前
一米阳光发布了新的文献求助10
22秒前
许雨青完成签到,获得积分20
22秒前
22秒前
千千完成签到,获得积分10
22秒前
小二郎应助phoenix001采纳,获得10
23秒前
天天快乐应助kanwenxian采纳,获得10
23秒前
23秒前
23秒前
贰叁发布了新的文献求助10
24秒前
李振博完成签到 ,获得积分10
25秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3970008
求助须知:如何正确求助?哪些是违规求助? 3514711
关于积分的说明 11175563
捐赠科研通 3250077
什么是DOI,文献DOI怎么找? 1795198
邀请新用户注册赠送积分活动 875630
科研通“疑难数据库(出版商)”最低求助积分说明 804931