Extracellular CIRP Upregulates Proinflammatory Cytokine Expression via the NF-kappaB and ERK1/2 Signaling Pathways in Psoriatic Keratinocytes.
Extracellular CIRP Upregulates Proinflammatory Cytokine Expression via the NF-kappaB and ERK1/2 Signaling Pathways in Psoriatic Keratinocytes.
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DOI：
10.1155/2022/5978271
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发表时间：
2022
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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银屑病是一种慢性炎症性皮肤病，促炎细胞因子水平的升高是银屑病发病机制的关键驱动因素。细胞外冷诱导RNA结合蛋白（eCIRP）已被证明在各种急性和慢性炎症性疾病中发挥作用。C23是一种源自CIRP的短肽，竞争性结合CIRP受体并减少炎性疾病中的损伤。然而，尚未研究eCIRP在银屑病中的作用。在本研究中，我们研究了eCIRP在角质形成细胞中促炎细胞因子表达中的作用。我们的数据显示，eCIRP表达在银屑病患者和咪喹莫特（IMQ-）诱导的银屑病小鼠的血清中以及用促炎细胞因子（IL-1α、IL-17 A、IL-22、制瘤素M和TNF-α;混合物M5）刺激的细胞中增加。重组人CIRP（rhCIRP）可促进培养角质形成细胞中促炎细胞因子TNF-α、IL-6和IL-8的表达以及NF-κ B（NF-κB）和ERK 1/2的活化。然后我们发现，eCIRP的上述作用可以在正常角质形成细胞和M5刺激的银屑病角质形成细胞中被C23阻断。此外，在体内实验中发现，C23可以有效地改善IMQ诱导的银屑病皮炎。C23处理的IMQ诱导的银屑病小鼠皮损中TNF-α和IL-6 mRNA表达降低，这种作用伴随着NF-κB和ERK 1/2信号通路的抑制。综上所述，eCIRP在银屑病发病机制中起重要作用，有可能成为银屑病治疗的新靶点。
Psoriasis is a chronic inflammatory skin disease, and elevation of proinflammatory cytokine levels is a critical driver of the pathogenesis of psoriasis. Extracellular cold-inducible RNA-binding protein (eCIRP) has been shown to play a role in various acute and chronic inflammatory diseases. C23, a short peptide derived from CIRP, competitively binds CIRP receptors and reduces damage in inflammatory diseases. However, the effect of eCIRP in psoriasis has not been studied. In the present study, we investigated the role of eCIRP in the expression of proinflammatory cytokines in keratinocytes. Our data show that eCIRP expression was increased in the sera of psoriasis patients and imiquimod- (IMQ-) induced psoriatic mice and cells stimulated with proinflammatory cytokines (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α; mix M5). Recombinant human CIRP (rhCIRP) promoted the expression of the proinflammatory cytokines TNF-α, IL-6, and IL-8 and the activation of NF-kappaB (NF-κB) and ERK1/2 in cultured keratinocytes. We then found that the above effects of eCIRP could be blocked by C23 in both normal keratinocytes and M5-stimulated psoriatic keratinocytes. In addition, in vivo experiments revealed that C23 could effectively ameliorate IMQ-induced psoriatic dermatitis. TNF-α and IL-6 mRNA expressions were reduced in the skin lesions of mice with C23-treated IMQ-induced psoriasis, and this effect was accompanied by inhibition of the NF-κB and ERK1/2 signaling pathways. In summary, eCIRP plays an important role in the pathogenesis of psoriasis and may become a new target for psoriasis treatment.
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DOI：
10.1097/shk.0000000000000988
发表时间：
2018-03
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
McGinn J;Zhang F;Aziz M;Yang WL;Nicastro J;Coppa GF;Wang P
通讯作者：
Wang P
富含甘氨酸的RNA结合蛋白，介导了对哺乳动物细胞生长的冷诱导抑制。
影响因子：
7.8
作者：
Nishiyama, H;Itoh, K;Kaneko, Y;Kishishita, M;Yoshida, O;Fujita, J
通讯作者：
Fujita, J
影响因子：
2.4
作者：
KRAGBALLE, K;IVERSEN, L
通讯作者：
IVERSEN, L
Cimifugin 通过 NF-κB/MAPK 通路抑制氧化应激和炎症，改善咪喹莫特诱导的牛皮癣
影响因子：
4
作者：
Liu, Aimin;Zhao, Wei;Wang, Qingxing
通讯作者：
Wang, Qingxing
影响因子：
6.5
作者：
Croxford, Andrew L.;Karbach, Susanne;Waisman, Ari
通讯作者：
Waisman, Ari