Secreted glucose regulated protein78 ameliorates DSS-induced mouse colitis.
Secreted glucose regulated protein78 ameliorates DSS-induced mouse colitis.
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分泌型葡萄糖调节蛋白78 可改善 DSS 诱导的小鼠结肠炎
DOI：
10.3389/fimmu.2023.986175
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
分泌形式的78 kda葡萄糖调节蛋白（sGRP78）因其帮助解决炎症的特性而被广泛报道。然而，人们对其治疗结肠炎的潜力知之甚少。为了研究GRP78在溃疡性结肠炎中的表达模式和功能结局，我们在人类和小鼠结肠炎样本中检测了GRP78的表达。研究发现，GRP78在肠道中自发高水平分泌，肠道是免疫耐受的生理部位。在dss诱导结肠炎的活动期，sGRP78水平显著降低，但在消退期迅速反弹，使其成为治疗结肠炎的潜在候选药物。在接下来的实验中，sGRP78被证明可以降低实验性结肠炎的易感性，表现为肠道症状的整体改善，TJ完整性的恢复，免疫细胞的浸润减少，炎症细胞因子的产生受损。内源性sGRP78特异性裂解可加重DSS结肠炎。过继性转移sgrp78条件BMDMs可减少肠道炎症。我们通过抑制tlr4依赖性map -激酶和NF-κB通路，将sGRP78治疗与巨噬细胞生物学改变和巨噬细胞偏斜极化联系起来。基于这些研究，sGRP78作为一种天然存在的免疫调节分子，可能是一种有吸引力的新型急性肠道炎症治疗剂。
The secreted form of 78-kDa glucose-regulated protein (sGRP78) has been widely reported for its property in aiding resolution of inflammatory. However, little is known on its potential in the treatment of colitis. To investigate the expression pattern and functional outcome of GRP78 in ulcerative colitis, its expression was measured in human and murine colitis samples. It was found that GRP78 was spontaneously secreted to a high level in gut, which is a physiological site of immune tolerance. During the active phase of DSS-induced colitis, the sGRP78 level was significantly reduced but rebounded quickly during resolving phase, making it a potential candidate for the treatment of colitis. In the following experiments, the administration of sGRP78 was proved to decrease susceptibility to experimental colitis, as indicated by an overall improvement of intestinal symptoms, restoration of TJ integrity, decreased infiltration of immune cells and impaired production of inflammatory cytokines. And specific cleavage of endogenous sGRP78 could aggravate DSS colitis. Adoptive transfer of sGRP78-conditioned BMDMs reduced inflammation in the gut. We linked sGRP78 treatment with altered macrophage biology and skewed macrophage polarization by inhibiting the TLR4-dependent MAP-kinases and NF-κB pathways. Based on these studies, as a naturally occurring immunomodulatory molecule, sGRP78 might be an attractive novel therapeutic agent for acute intestinal inflammation.
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影响因子：
3.7
作者：
Schröder-Braunstein J;Gras J;Brors B;Schwarz S;Szikszai T;Lasitschka F;Wabnitz G;Heidtmann A;Lee YS;Schiessling S;Leowardi C;Al-Saeedi M;Ulrich A;Engelke A;Winter J;Samstag Y;Giese T;Meuer S
通讯作者：
Meuer S
影响因子：
2.7
作者：
Jiang, Qing;Sun, Yuanli;Shen, Guanxin
通讯作者：
Shen, Guanxin
影响因子：
46.9
作者：
Chen HJ;Wei Z;Sun J;Bhattacharya A;Savage DJ;Serda R;Mackeyev Y;Curley SA;Bu P;Wang L;Chen S;Cohen-Gould L;Huang E;Shen X;Lipkin SM;Copeland NG;Jenkins NA;Shuler ML
通讯作者：
Shuler ML
影响因子：
29.7
作者：
Kaser A;Zeissig S;Blumberg RS
通讯作者：
Blumberg RS
影响因子：
--
作者：
Brownlie, RJ;Myers, LK;Thompson, SJ
通讯作者：
Thompson, SJ