Complement component 3 prevents imiquimod-induced psoriatic skin inflammation by inhibiting apoptosis in mice.

Complement component 3 prevents imiquimod-induced psoriatic skin inflammation by inhibiting apoptosis in mice.
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补体成分 3 通过抑制小鼠细胞凋亡来预防咪喹莫特诱导的银屑病皮肤炎症。

DOI:
10.1016/j.intimp.2020.106692
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发表时间:
2020-06
影响因子:
5.6
通讯作者:
Xu Gui-Lian
Xu Gui-Lian
中科院分区:
医学2区
文献类型:
--
作者:
Zheng Quan-You;Liang Shen-Ju;Xu Feng;Yang Yi;Feng Jian-Li;Shen Fen;Zhong Yu;Wu Shun;Shu Yong;Sun Dao-Dong;Xu Gui-Lian

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补体成分 3 (C3) 是补体系统中的关键分子,是包括牛皮癣在内的多种疾病的重要免疫介质。然而,C3 在银屑病病理和发展中的机制作用仍然难以捉摸。在这里,我们发现 C3 缺乏显着增强了咪喹莫特诱导的银屑病样皮肤炎症,其特征是比野生型对应物有更大的表皮增生、炎症细胞浸润和炎症基因表达。此外,C3 缺乏促进了咪喹莫特诱导的皮肤细胞凋亡,并支持发炎组织中更大比例的 IFN-γ+T 细胞。因此,C3 缺乏小鼠中的 C3 补充可减少皮肤炎症和细胞凋亡。此外,用 Z-VAD-FMK(一种广泛的 caspase 抑制剂)阻断细胞凋亡,可显着减弱 C3 缺陷小鼠中咪喹莫特诱导的银屑病样皮肤炎症和 IFN-γ+T 细胞反应。总的来说,我们的结果表明 C3 通过抑制细胞凋亡来预防咪喹莫特诱导的银屑病样皮肤炎症。
Complement component 3 (C3), a pivotal molecule in the complement system, is an essential immune mediator in various diseases, including psoriasis. However, the mechanistic role of C3 in psoriasis pathology and development remains elusive. Here, we showed that C3 deficiency dramatically augmented imiquimod-induced psoriasis-like skin inflammation, characterized by greater epidermal hyperplasia, inflammatory cell infiltration, and inflammatory gene expression than those in wild-type counterparts. In addition, C3 deficiency promoted imiquimod-induced skin cell apoptosis and supported greater proportions of IFN-γ+T cells in the inflamed tissues. Accordingly, C3 supplement in the C3 deficient mice reduced skin inflammation and cells apoptosis. Moreover, blocking apoptosis with Z-VAD-FMK, a broad caspase inhibitor, markedly attenuated imiquimod-induced psoriasis-like skin inflammation and IFN-γ+T cell responses in C3-deficient mice. Collectively, our results suggest that C3 prevents imiquimod-induced psoriasis-like skin inflammation by inhibiting apoptosis.
DOI: 10.4049/jimmunol.1302787
发表时间: 2014-08-01
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Mueller-Ortiz SL;Morales JE;Wetsel RA
通讯作者: Wetsel RA
DOI: 10.4049/jimmunol.0801191
发表时间: 2009-09-01
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Nakayama Y;Kim SI;Kim EH;Lambris JD;Sandor M;Suresh M
通讯作者: Suresh M
DOI: 10.1111/j.1346-8138.2010.01037.x
发表时间: 2010-09
期刊: The Lancet
影响因子: --
作者:
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DOI: 10.1101/cshperspect.a015354
发表时间: 2014-08-01
影响因子: 5.4
作者:
Di Meglio, Paola;Villanova, Federica;Nestle, Frank O.
通讯作者: Nestle, Frank O.
DOI: 10.1111/j.1365-2249.2009.03896.x
发表时间: 2009-05-01
影响因子: 4.6
作者:
Gullstrand, B.;Martensson, U.;Truedsson, L.
通讯作者: Truedsson, L.