<br>CWHM-12 是整合素介导的转化生长因子-β 激活的拮抗剂，可在小鼠早期结核分枝杆菌感染期间提供保护,Journal of Interferon & Cytokine Research

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CWHM-12 是整合素介导的转化生长因子-β 激活的拮抗剂，可在小鼠早期结核分枝杆菌感染期间提供保护
Journal of Interferon & Cytokine Research ( IF 1.9 ) Pub Date : 2022-08-18 , DOI: 10.1089/jir.2022.0027
Ninecia R Scott ₁ , Shyamala Thirunavukkarasu ₁ , Javier Rangel-Moreno ₂ , David W Griggs ₃ , Shabaana A Khader ₁

Affiliation

结核病（TB）由致病菌结核分枝杆菌（ Mtb ）引起，是世界上最致命的传染病之一。目前，被批准用于对抗结核病的疫苗卡介苗并不能提供针对该疾病的完全保护，因此需要开发新的疗法来治疗这种感染。转化生长因子β（TGF-β）的过度表达与肺促纤维化变化相关。分泌的无活性 TGF-β 通过 αv 整合素的裂解和释放而被激活。整合素介导的 TGF-β 调节被认为是促纤维化过程中的主开关和潜在的治疗靶点。因此，在这项研究中，我们试图确定在高度易感Mtb感染小鼠模型（即 C3Heb/FeJ）中，使用广泛的整合素拮抗剂 CWHM-12 进行治疗是否能够抑制肺纤维化并增强Mtb控制。（FeJ）。 Mtb感染早期阶段的 CWHM-12 治疗可有效减轻疾病严重程度和与 iNOS、MIP-2 和 IL-10 产生减少相关的炎症，且不会降解胶原蛋白。这表明 CWHM-12 靶向 TGF-β 作为早期Mtb感染的辅助治疗的潜力。

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CWHM-12, an Antagonist of Integrin-Mediated Transforming Growth Factor-Beta Activation Confers Protection During Early Mycobacterium tuberculosis Infection in Mice

Tuberculosis (TB) caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb) is one of the most lethal infectious diseases in the world. Presently, Bacillus Calmette-Guerin, the vaccine approved for use against TB, does not offer complete protection against the disease, which necessitates the development of new therapeutics to treat this infection. Overexpression of transforming growth factor beta (TGF-β) is associated with pulmonary profibrotic changes. The inactive TGF-β secreted is activated through its cleavage and release by αv integrins. Integrin-mediated regulation of TGF-β is considered as a master switch in the profibrotic process and a potential therapeutic target. Thus, in this study, we sought to determine if treatment with a broad range antagonist of integrins, CWHM-12, has the potency to inhibit pulmonary fibrosis and enhance Mtb control in a highly susceptible mouse model of Mtb infection, namely the C3Heb/FeJ (FeJ). CWHM-12 treatment at the early stages of Mtb infection was efficacious in reducing disease severity and inflammation associated with decreased iNOS, MIP-2, and IL-10 production without degradation of collagen. This suggests a potential for CWHM-12 targeting of TGF-β to be explored as an adjunct therapeutic for early Mtb infection.

更新日期：2022-08-19

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