Immunomodulatory Activity of Diterpenes over Innate Immunity and Cytokine Production in a Human Alveolar Epithelial Cell Line Infected with Mycobacterium tuberculosis.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Alejandro David Hernández-Herrera, Julieta Luna-Herrera, Marisela Del Rocío González-Martínez, Adria I Prieto-Hinojosa, Ana Monica Turcios-Esquivel, Irais Castillo-Maldonado, Dealmy Delgadillo-Guzmán, Agustina Ramírez-Moren, Celia Bustos-Brito, Baldomero Esquivel, María-Del-Carmen Vega-Menchaca, David Pedroza-Escobar
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Abstract

Background: Mexico has the largest number of the genus salvia plant species, whose main chemical compounds of this genus are diterpenes, these chemical compounds have shown important biological activities such as: antimicrobial, anti-inflammatory and immunomodulatory.

Objective: This study aimed to evaluate the immunomodulatory activity of three diterpenes: 1) icetexone, 2) anastomosine and 3) 7,20-dihydroanastomosine, isolated from Salvia ballotiflora, over innate immunity and cytokine production in a human alveolar epithelial cell line infected with Mycobacterium tuberculosis.

Methods: The immunomodulatory activity of diterpenes over innate immunity included reactive oxygen and nitrogen species (ROS and RNS) induction in response to infection; cytokine production included TNF-α and TGF-β induction in response to infection.

Results: The diterpenes anastomosine and 7,20-dihydroanastomosine showed a statically significant (p < 0.01) increase of RNS after 36 h of infection and treatment of 2.0 μg/mL. Then, the ROS induction in response to infection showed a consistent statically significant (p < 0.01) increase after 12 h of diterpenes treatments. The cell cultures showed an anti-inflammatory effect, in the case of TGF-β induction, in response to infection when treated with the diterpenes. On the other hand, there was not any significant effect on TNF-α release.

Conclusion: The diterpenes anastomosine and 7,20-dihydroanastomosine increased the production of RNS after 36 h of infection and treatment. Besides, the three diterpenes increased the production of ROS after 12 h. This RNS and ROS modulation can be considered as an in vitro correlation of innate immunity in response to Mycobacterium tuberculosis infection; and an indicator of the damage of epithelial lung tissue. This study also showed an anti-inflammatory immune response by means of TGF-β modulation when compared with control group.

二萜对感染结核分枝杆菌的人肺泡上皮细胞系先天免疫和细胞因子产生的免疫调节活性。
背景:墨西哥是鼠尾草属植物种类最多的国家,鼠尾草属植物的主要化合物为二萜,这些化合物具有抗菌、抗炎和免疫调节等重要的生物活性。目的:研究丹参中三种二萜:1)冰替酮、2)吻合核苷和3)7,20-二氢吻合核苷对感染结核分枝杆菌的人肺泡上皮细胞系的免疫调节活性和细胞因子的产生。方法:二萜对先天免疫的免疫调节作用包括对感染反应的活性氧和活性氮(ROS和RNS)诱导;细胞因子的产生包括TNF-α和TGF-β诱导。结果:二萜吻合苷和7,20-二氢吻合苷在感染36 h及2.0 μg/mL处理后RNS升高有统计学意义(p < 0.01)。二萜处理12 h后,ROS诱导率呈显著升高(p < 0.01)。在TGF-β诱导的情况下,细胞培养物在用二萜处理感染时显示出抗炎作用。另一方面,对TNF-α释放无明显影响。结论:二萜吻合酶和7,20-二氢吻合酶在感染和治疗36 h后可增加RNS的产生。此外,三种二萜在12 h后增加了ROS的产生。这种RNS和ROS的调节可以被认为是对结核分枝杆菌感染的先天免疫应答的体外相关性;也是肺上皮组织损伤的一个指标。与对照组相比,本研究还显示通过TGF-β调节的抗炎免疫反应。
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来源期刊
Current molecular pharmacology
Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
4.90
自引率
3.70%
发文量
112
期刊介绍: Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.
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