Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skin.
Interleukin-33 increases antibacterial defense by activation of inducible nitric oxide synthase in skin.
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Interleukin-33 通过激活皮肤中的诱导型一氧化氮合酶来增强抗菌防御
DOI：
10.1371/journal.ppat.1003918
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发表时间：
2014-02
期刊：
影响因子：
6.7
通讯作者：
Lai Y
中科院分区：
文献类型：
--
作者：
Li C;Li H;Jiang Z;Zhang T;Wang Y;Li Z;Wu Y;Ji S;Xiao S;Ryffel B;Radek KA;Xia Z;Lai Y
白细胞介素-33（IL-33）与多种疾病相关，包括哮喘、类风湿性关节炎、组织损伤和感染。虽然IL-33已被指示参与金黄色葡萄球菌（S.金黄色葡萄球菌）伤口感染，关于IL-33如何被调节为增加宿主对皮肤细菌感染的防御的机制知之甚少。为了探索潜在的复杂机制，我们首先评估了IL-33在来自S.感染金黄色葡萄球菌的人类患者与正常对照组相比，S.金黄色葡萄球菌感染的患者我们接下来开发了一个S。金黄色葡萄球菌皮肤感染小鼠模型，发现IL-33在感染小鼠皮肤的真皮巨噬细胞中显著增加。由于葡萄球菌肽聚糖（PGN）和脂磷壁酸（LTA）不能诱导Tlr 2缺陷的腹腔巨噬细胞表达IL-33，因此PGN和LTA通过激活Toll样受体2（TLR 2）-丝裂原活化蛋白激酶（MAPK）-AKT-信号转导子和转录激活子3（STAT 3）信号通路诱导巨噬细胞表达IL-33，而MAPK，AKT，STAT 3抑制剂显著降低PGN或LTA诱导的IL-33。IL-33反过来作用于巨噬细胞以诱导杀微生物的一氧化氮（NO）释放。这种诱导依赖于诱导型一氧化氮合酶（iNOS）的活化，因为用iNOS抑制剂氨基胍处理巨噬细胞显著降低了IL-33诱导的NO释放。此外，氨基胍显著阻断IL-33抑制S.金黄色葡萄球菌，和IL-33沉默在巨噬细胞中显着增加S.金黄色葡萄球菌。此外，IL-33中和抗体的小鼠皮肤给药减少了iNOS的产生，但增加了S。皮肤金黄色。这些发现表明IL-33可以促进真皮巨噬细胞的抗菌能力，从而增强对皮肤细菌感染的抗菌防御。
Interleukin-33 (IL-33) is associated with multiple diseases, including asthma, rheumatoid arthritis, tissue injuries and infections. Although IL-33 has been indicated to be involved in Staphylococcus aureus (S. aureus) wound infection, little is known about how IL-33 is regulated as a mechanism to increase host defense against skin bacterial infections. To explore the underlying intricate mechanism we first evaluated the expression of IL-33 in skin from S. aureus-infected human patients. Compared to normal controls, IL-33 was abundantly increased in skin of S. aureus-infected patients. We next developed a S. aureus cutaneous infection mouse model and found that IL-33 was significantly increased in dermal macrophages of infected mouse skin. The expression of IL-33 by macrophages was induced by staphylococcal peptidoglycan (PGN) and lipoteichoic acid (LTA) via activation of toll-like receptor 2(TLR2) –mitogen-activated protein kinase (MAPK)-AKT-signal transducer and activator of transcription 3(STAT3) signaling pathway as PGN and LTA failed to induce IL-33 in Tlr2-deficient peritoneal macrophages, and MAPK,AKT, STAT3 inhibitors significantly decreased PGN- or LTA-induced IL-33. IL-33, in turn, acted on macrophages to induce microbicidal nitric oxygen (NO) release. This induction was dependent on inducible nitric oxide synthase (iNOS) activation, as treatment of macrophages with an inhibitor of iNOS, aminoguanidine, significantly decreased IL-33-induced NO release. Moreover, aminoguanidine significantly blocked the capacity of IL-33 to inhibit the growth of S. aureus, and IL-33 silencing in macrophages significantly increased the survival of S. aureus in macrophages. Furthermore, the administration of IL-33-neutralizing antibody into mouse skin decreased iNOS production but increased the survival of S. aureus in skin. These findings reveal that IL-33 can promote antimicrobial capacity of dermal macrophages, thus enhancing antimicrobial defense against skin bacterial infections.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
DOI：
10.4049/jimmunol.1003020
发表时间：
2011-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kouzaki H;Iijima K;Kobayashi T;O'Grady SM;Kita H
通讯作者：
Kita H
抗菌蛋白REG3A调节皮肤损伤后角质形成细胞增殖和分化。
影响因子：
32.4
作者：
Lai Y;Li D;Li C;Muehleisen B;Radek KA;Park HJ;Jiang Z;Li Z;Lei H;Quan Y;Zhang T;Wu Y;Kotol P;Morizane S;Hata TR;Iwatsuki K;Tang C;Gallo RL
通讯作者：
Gallo RL
影响因子：
2.9
作者：
Ghaffari, Abdi;Jalili, Reza;Ghahary, Aziz
通讯作者：
Ghahary, Aziz
影响因子：
4.4
作者：
Kurowska-Stolarska, Mariola;Kewin, Pete;Xu, Damo
通讯作者：
Xu, Damo