Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis.
Inhibition of gamma-secretase activity without interfering in Notch signalling decreases inflammatory response in patients with cutaneous leishmaniasis.
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DOI：
10.1080/22221751.2021.1932608
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Carvalho LP
中科院分区：
文献类型：
--
作者：
Nascimento MT;Franca M;Carvalho AM;Amorim CF;Peixoto F;Beiting D;Scott P;Carvalho EM;Carvalho LP
皮肤利什曼病（CL）患者呈现与组织损伤和溃疡发展相关的加剧的炎症反应。越来越多的患者表现出治疗失败，这仍然没有得到很好的理解。我们假设辅助抗炎治疗对CL患者有益。本研究的目的是研究Notch信号传导和γ-分泌酶活性对CL患者中观察到的炎症反应的贡献。Notch信号传导是动物物种中保守的分子信号传导途径。γ-分泌酶形成蛋白质复合物，其在其他途径中调节Notch信号传导和免疫应答。我们发现，Notch 1细胞受体信号传导可防止病理性炎症反应，而JLK 6（一种不干扰Notch信号传导的γ-分泌酶抑制剂）可降低CL的体外炎症反应。我们的数据表明，JLK 6可能作为一种辅助治疗CL患者。
Cutaneous leishmaniasis (CL) patients present an exacerbated inflammatory response associated with tissue damage and ulcer development. Increasing numbers of patients have exhibited treatment failure, which remains not well understood. We hypothesized that adjuvant anti-inflammatory therapy would benefit CL patients. The aim of the present study was to investigate the contribution of Notch signalling and gamma-secretase activity to the inflammatory response observed in CL patients. Notch signalling is a molecular signalling pathway conserved among animal species. Gamma-secretase forms a complex of proteins that, among other pathways, modulates Notch signalling and immune response. We found that Notch 1 cell receptor signalling protects against the pathologic inflammatory response, and JLK6, a gamma-secretase inhibitor that does not interfere with Notch signalling, was shown to decrease the in-vitro inflammatory response in CL. Our data suggest that JLK6 may serve as an adjuvant treatment for CL patients.
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影响因子：
6.7
作者：
Novais, Fernanda O.;Carvalho, Augusto M.;Scott, Phillip
通讯作者：
Scott, Phillip
影响因子：
6.4
作者：
Campos, Tais M.;Novais, Fernanda O.;Carvalho, Lucas P.
通讯作者：
Carvalho, Lucas P.
DOI：
10.4269/ajtmh.1986.35.79
发表时间：
1986-01-01
影响因子：
3.3
作者：
REED, SG;BADARO, R;JONES, TC
通讯作者：
JONES, TC
影响因子：
7.3
作者：
Carvalho LP;Passos S;Schriefer A;Carvalho EM
通讯作者：
Carvalho EM
影响因子：
5.4
作者：
Monsalve, Eva;Ruiz-Garcia, Almudena;Diaz-Guerra, Maria Jose M.
通讯作者：
Diaz-Guerra, Maria Jose M.