Matsuura Tetsuhiko, Sato Masaaki, Nagai Kouhei, Sato Toshiyuki, Arito Mitsumi, Omoteyama Kazuki, Suematsu Naoya, Okamoto Kazuki, Kato Tomohiro, Soma Yoshinao, Kurokawa Manae S
Department of Dermatology, St. Marianna University School of Medicine, Japan.
Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Japan.
J Dermatol Sci. 2017 Jul;87(1):36-49. doi: 10.1016/j.jdermsci.2017.03.014. Epub 2017 Mar 27.
Psoriasis is a refractory inflammatory disease, however, its pathophysiology is still not fully understood.
We tried to identify novel serum peptides associated with the pathophysiology of psoriasis.
Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23 healthy control (HC) subjects were analyzed by mass spectrometry. The effects of some peptides on the secretion of humoral factors from dermal cells were investigated by cytokine arrays and ELISAs.
A total of 93 peptides were detected. 24, 20, 23, and 2 peptides showed at least 1.2-fold difference in ion intensity between the psoriasis (PV+PsA) and HC groups, between the PV+PsA and AD groups, between the PV and PsA groups, and between patients with severe-to-moderate PV (n=6) and those with mild PV (n=18), respectively (p<0.05). 13 out of 27 peptides that showed at least 1.5-fold ion intensity difference in the abovementioned 4 comparisons were identified. The parent proteins of the identified peptides included a coagulation factor, proteins involved in the maintenance of skin, and a protein relating to cytoskeleton. We focused on 2 peptides that were increased in the PV+PsA group: a fibrinogen α chain-derived peptide (1462m/z), the unmodified form of which was fibrinopeptide A-des-alanine (FPAdA), and a filaggrin (FLG)-derived peptide (1977m/z), a modified form of FLG (QpE, QE; FLG-pEE). FPAdA stimulation increased the secretion of GROα from dermal microvascular endothelial cells (dMVECs) and decreased the secretion of lipocalin-2 from keratinocytes in comparison to FPAdA-resequenced peptide stimulation (GROα, 280.9±7.3pg/mL vs. 229.6±5.0pg/mL, p<0.001; lipocalin-2, 273±13pg/mL vs. 350±10pg/mL, p<0.01). Interestingly, FLG-pEE stimulation decreased the secretion of GROα, IL-8, and MCP-1 from dMVECs in comparison to FLG-derived control peptide stimulation (GROα, 844.3±47.5pg/mL vs. 1038.5±96.9pg/mL, p<0.05; IL-8, 2240.1±172.6pg/mL vs. 3221.8±523.7pg/mL, p<0.05; MCP-1, 4057.8±157.2pg/mL vs. 4619.1±213.4pg/mL, p<0.05).
The results suggested that some serum peptides are involved in the pathophysiology of psoriasis, regulating the secretion of inflammatory chemokines and an antimicrobial protein. The modulation of serum peptides may be a potential therapeutic strategy for psoriasis.
银屑病是一种难治性炎症性疾病，然而其病理生理学仍未完全阐明。
我们试图鉴定与银屑病病理生理学相关的新型血清肽。
采用质谱分析法对24例寻常型银屑病（PV）患者、10例银屑病关节炎（PsA）患者、14例特应性皮炎（AD）患者和23例健康对照（HC）受试者的血清肽进行分析。通过细胞因子阵列和酶联免疫吸附测定法研究了某些肽对真皮细胞体液因子分泌的影响。
共检测到93种肽。分别有24种、20种、23种和2种肽在银屑病（PV+PsA）组与HC组之间、PV+PsA组与AD组之间、PV组与PsA组之间以及中重度PV患者（n=6）与轻度PV患者（n=18）之间的离子强度至少有1.2倍差异（p<0.05）。在上述4项比较中，离子强度差异至少为1.5倍的27种肽中有13种被鉴定出来。已鉴定肽的母体蛋白包括一种凝血因子、参与维持皮肤的蛋白质以及一种与细胞骨架相关的蛋白质。我们重点关注PV+PsA组中增加的2种肽：一种纤维蛋白原α链衍生肽（1462m/z），其未修饰形式为纤维蛋白肽A-去丙氨酸（FPAdA），以及一种丝聚蛋白（FLG）衍生肽（1977m/z），即FLG的修饰形式（QpE、QE；FLG-pEE）。与FPAdA重测序肽刺激相比，FPAdA刺激可增加真皮微血管内皮细胞（dMVECs）中GROα的分泌，并减少角质形成细胞中lipocalin-2的分泌（GROα，280.9±7.3pg/mL对229.6±5.0pg/mL，p<0.001；lipocalin-2，273±13pg/mL对350±10pg/mL，p<0.01）。有趣的是，与FLG衍生的对照肽刺激相比，FLG-pEE刺激可减少dMVECs中GROα、IL-8和MCP-1的分泌（GROα，844.3±47.5pg/mL对1038.5±96.9pg/mL，p<0.05；IL-8，2240.1±172.6pg/mL对3221.8±523.7pg/mL，p<0.05；MCP-1，4057.8±157.2pg/mL对4619.1±213.4pg/mL，p<0.05）。
结果表明，一些血清肽参与银屑病的病理生理学过程，调节炎症趋化因子和一种抗菌蛋白的分泌。血清肽的调节可能是银屑病的一种潜在治疗策略。
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