Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.
Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.
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DOI：
10.1038/s41551-023-01025-1
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发表时间：
2023-09
影响因子：
28.1
通讯作者：
中科院分区：
文献类型：
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作者：
用全身给予的抗炎治疗来治疗慢性炎症与中度至重度副作用相关，并且局部给予的药物的功效是短暂的。在这里，我们表明，炎症可以局部抑制免疫抑制酶吲哚胺2，3-双加氧酶1（IDO）和半乳糖凝集素-3（Gal 3）的融合蛋白。Gal 3将IDO锚定至组织，限制IDO-Gal 3远离注射部位的扩散。在内毒素诱导的炎症、银屑病、牙周病和骨关节炎的啮齿动物模型中，融合蛋白在注射后在发炎组织和关节中保留约1周，并且动物中局部炎症、疾病进展和炎性疼痛的改善伴随着组织的稳态保存和不存在整体免疫抑制。IDO-Gal 3可作为免疫调节酶用于控制其它炎性病症中的局灶性炎症。与组织锚定蛋白融合并注射到发炎组织中的抗炎酶可改善局部炎症，而不会引起全身性免疫抑制，如多种炎性疾病的啮齿动物模型所示。
The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site. In rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis, the fusion protein remained in the inflamed tissues and joints for about 1 week after injection, and the amelioration of local inflammation, disease progression and inflammatory pain in the animals were concomitant with homoeostatic preservation of the tissues and with the absence of global immune suppression. IDO-Gal3 may serve as an immunomodulatory enzyme for the control of focal inflammation in other inflammatory conditions. An anti-inflammatory enzyme fused with a tissue-anchoring protein and injected into inflamed tissues ameliorates local inflammation without causing systemic immune suppression, as shown in multiple rodent models of inflammatory diseases.
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抗炎药治疗骨关节炎的研究：环氧酶-2抑制剂和类固醇。
影响因子：
--
作者：
Cho H;Walker A;Williams J;Hasty KA
通讯作者：
Hasty KA
影响因子：
3
作者：
Ochieng, J;Furtak, V;Lukyanov, P
通讯作者：
Lukyanov, P
DOI：
10.1084/jem.189.9.1363
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Munn DH;Shafizadeh E;Attwood JT;Bondarev I;Pashine A;Mellor AL
通讯作者：
Mellor AL
影响因子：
3
作者：
Delitto, Andrea E.;Rocha, Fernanda;Wallet, Shannon M.
通讯作者：
Wallet, Shannon M.
影响因子：
9.7
作者：
Kitajima, Takashi;Sakuragi, Makoto;Ito, Yoshihiro
通讯作者：
Ito, Yoshihiro