{"title":"干扰素α-2b对视网膜色素上皮细胞凋亡、炎症、血管生成和神经保护基因表达的体外研究","authors":"Mehrdad Afarid, Hossein Bahari, Fatemeh Sanie-Jahromi","doi":"10.1089/jir.2023.0028","DOIUrl":null,"url":null,"abstract":"<p><p>Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the <i>in vitro</i> effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (<i>BCL-2</i>, <i>BAX</i>, <i>BDNF</i>, <i>VEGF</i>, and <i>IL-1b</i>) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of <i>BCL-2</i>, <i>BAX</i>, <i>BDNF</i>, and <i>IL-1b</i>; however, the <i>BCL-2/BAX</i> ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that <i>VEGF</i> expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe (<i>BCL-2/BAX</i> ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 7","pages":"299-306"},"PeriodicalIF":1.9000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>In Vitro</i> Evaluation of Apoptosis, Inflammation, Angiogenesis, and Neuroprotection Gene Expression in Retinal Pigmented Epithelial Cell Treated with Interferon α-2b.\",\"authors\":\"Mehrdad Afarid, Hossein Bahari, Fatemeh Sanie-Jahromi\",\"doi\":\"10.1089/jir.2023.0028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the <i>in vitro</i> effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (<i>BCL-2</i>, <i>BAX</i>, <i>BDNF</i>, <i>VEGF</i>, and <i>IL-1b</i>) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of <i>BCL-2</i>, <i>BAX</i>, <i>BDNF</i>, and <i>IL-1b</i>; however, the <i>BCL-2/BAX</i> ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that <i>VEGF</i> expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe (<i>BCL-2/BAX</i> ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.</p>\",\"PeriodicalId\":16261,\"journal\":{\"name\":\"Journal of Interferon and Cytokine Research\",\"volume\":\"43 7\",\"pages\":\"299-306\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Interferon and Cytokine Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/jir.2023.0028\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Interferon and Cytokine Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jir.2023.0028","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
血管生成、视网膜神经病变和炎症是糖尿病视网膜病变(DR)的主要分子特征,应考虑到潜在的治疗方法。视网膜色素上皮细胞(RPE)在DR的进展中起主要作用。本研究评估干扰素(IFN) α-2b在体外对RPE细胞凋亡、炎症、神经保护和血管生成相关基因表达的影响。RPE细胞与IFN α-2b共培养,剂量分别为500和1000 IU,处理时间分别为24和48 h。通过实时聚合酶链反应(real-time polymerase chain reaction, PCR)评估处理细胞与对照细胞中基因(BCL-2、BAX、BDNF、VEGF和IL-1b)的定量相对表达。本研究结果表明,1000 IU (48 h)的IFN治疗导致BCL-2、BAX、BDNF和IL-1b的显著上调;然而,在任何治疗模式下,BCL-2/BAX比值从1:1没有统计学变化。我们还发现,在RPE细胞中,500 IU处理24小时,VEGF表达下调。由此可见,IFN α-2b是安全的(BCL-2/BAX ~ 1:1),并在1,000 IU (48 h)时增强神经保护作用;同时,ifn α-2b诱导RPE细胞发生炎症。此外,IFN α-2b仅在500 IU (24 h)处理的RPE细胞中观察到抗血管生成作用。IFN α-2b在低剂量、短持续时间下具有抗血管生成作用,而在高剂量、长持续时间下具有神经保护和炎症作用。因此,应根据疾病的类型和分期考虑适当的治疗浓度和持续时间,以取得干扰素治疗的成功。
In Vitro Evaluation of Apoptosis, Inflammation, Angiogenesis, and Neuroprotection Gene Expression in Retinal Pigmented Epithelial Cell Treated with Interferon α-2b.
Angiogenesis, retinal neuropathy, and inflammation are the main molecular features of diabetic retinopathy (DR) and should be taken into consideration for potential treatment approaches. Retinal pigmented epithelial (RPE) cells play a major role in DR progression. This study evaluated the in vitro effect of interferon (IFN) α-2b on the expression of genes involved in apoptosis, inflammation, neuroprotection, and angiogenesis in RPE cells. RPE cells were cocultured with IFN α-2b at 2 doses (500 and 1,000 IU) and treatment periods (24 and 48 h). The quantitative relative expression of genes (BCL-2, BAX, BDNF, VEGF, and IL-1b) was evaluated in the treated versus control cells through real-time polymerase chain reaction (PCR). The result of this study demonstrated that IFN treatment at 1,000 IU (48 h) led to significant upregulation of BCL-2, BAX, BDNF, and IL-1b; however, the BCL-2/BAX ratio was not statistically altered from 1:1, in any of the treatment patterns. We also showed that VEGF expression was downregulated in RPE cells treated with 500 IU for 24 h. It can be concluded that IFN α-2b was safe (BCL-2/BAX ∼1:1) and enhanced neuroprotection at 1,000 IU (48 h); however-at the same time-IFN α-2b induced inflammation in RPE cells. Moreover, the antiangiogenic effect of IFN α-2b was solely observed in RPE cells treated with 500 IU (24 h). It seems that IFN α-2b in lower doses and short duration exerts antiangiogenic effects and in higher doses and longer duration has neuroprotective and inflammatory effects. Hence, appropriate concentration and duration of treatment, according to the type and stage of the disease, should be considered to achieve success in IFN therapy.
期刊介绍:
Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.