Mario Brito da Silva Filho , Gabriela Aniceto , Patrícia Maria Fernandes , Iara Gonçalves Aquino , Gustavo Duarte Mendes , Marcelo Henrique Napimoga , Juliana Trindade Clemente-Napimoga , Henrique Ballassini Abdalla
{"title":"肉毒杆菌毒素 A 可抑制 BV-2 小胶质细胞的炎症反应。","authors":"Mario Brito da Silva Filho , Gabriela Aniceto , Patrícia Maria Fernandes , Iara Gonçalves Aquino , Gustavo Duarte Mendes , Marcelo Henrique Napimoga , Juliana Trindade Clemente-Napimoga , Henrique Ballassini Abdalla","doi":"10.1016/j.toxicon.2024.108182","DOIUrl":null,"url":null,"abstract":"<div><div>Our previous studies have demonstrated the analgesic effects of botulinum toxin type A (BoNT/A) in a pre-clinical model of rheumatoid arthritis of the temporomandibular joint, where we proposed that BoNT/A decreases the neurogenic milieu after reaching the subnucleus caudalis. However, it is unknown whether BoNT/A directly regulates microglial cell activity. Therefore, the present study investigates the effects of BoNT/A on a microglial murine cell lineage (BV-2) in different inflammatory conditions. Cellular viability and proliferation were carried out with different concentrations of BoNT/A (ranging from 0.3125 to 20 U/mL) for 24 h. Cells were primed with carrageenan (300 μg/mL) or Lipopolysaccharides (LPS) (20 ng/mL). The gene expression of IL-1β, IL-6, IL-18, TNF-α, Ikkβ, p65, Iba1 were quantified using PCR-RT. The supernatant was used to determine IL-1β, IL-6, and TNF-α levels. For all data, the significance level was set at 5%. Overall, data analysis revealed that BoNT/A 1.25 U/mL exhibited the greatest effect cell viability and proliferation. In addition, genes associated with inflammatory response in both stimuli (carrageenan and LPS) were downregulated in the presence of BoNT/A. Lastly, BoNT/A mitigates the protein levels of IL-1β and TNF-α in a time and dose-dependent manner. In conclusion, our results revealed that BoNT/A directly modulates the microglial cells' activities in an inflammatory context, opening new perspectives for using BoNT/A, considering its potential immunomodulatory effect.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"252 ","pages":"Article 108182"},"PeriodicalIF":2.6000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Botulinum toxin A dampened inflammatory response in BV-2 microglial cells\",\"authors\":\"Mario Brito da Silva Filho , Gabriela Aniceto , Patrícia Maria Fernandes , Iara Gonçalves Aquino , Gustavo Duarte Mendes , Marcelo Henrique Napimoga , Juliana Trindade Clemente-Napimoga , Henrique Ballassini Abdalla\",\"doi\":\"10.1016/j.toxicon.2024.108182\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Our previous studies have demonstrated the analgesic effects of botulinum toxin type A (BoNT/A) in a pre-clinical model of rheumatoid arthritis of the temporomandibular joint, where we proposed that BoNT/A decreases the neurogenic milieu after reaching the subnucleus caudalis. However, it is unknown whether BoNT/A directly regulates microglial cell activity. Therefore, the present study investigates the effects of BoNT/A on a microglial murine cell lineage (BV-2) in different inflammatory conditions. Cellular viability and proliferation were carried out with different concentrations of BoNT/A (ranging from 0.3125 to 20 U/mL) for 24 h. Cells were primed with carrageenan (300 μg/mL) or Lipopolysaccharides (LPS) (20 ng/mL). The gene expression of IL-1β, IL-6, IL-18, TNF-α, Ikkβ, p65, Iba1 were quantified using PCR-RT. The supernatant was used to determine IL-1β, IL-6, and TNF-α levels. For all data, the significance level was set at 5%. Overall, data analysis revealed that BoNT/A 1.25 U/mL exhibited the greatest effect cell viability and proliferation. In addition, genes associated with inflammatory response in both stimuli (carrageenan and LPS) were downregulated in the presence of BoNT/A. Lastly, BoNT/A mitigates the protein levels of IL-1β and TNF-α in a time and dose-dependent manner. In conclusion, our results revealed that BoNT/A directly modulates the microglial cells' activities in an inflammatory context, opening new perspectives for using BoNT/A, considering its potential immunomodulatory effect.</div></div>\",\"PeriodicalId\":23289,\"journal\":{\"name\":\"Toxicon\",\"volume\":\"252 \",\"pages\":\"Article 108182\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicon\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0041010124007542\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041010124007542","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Botulinum toxin A dampened inflammatory response in BV-2 microglial cells
Our previous studies have demonstrated the analgesic effects of botulinum toxin type A (BoNT/A) in a pre-clinical model of rheumatoid arthritis of the temporomandibular joint, where we proposed that BoNT/A decreases the neurogenic milieu after reaching the subnucleus caudalis. However, it is unknown whether BoNT/A directly regulates microglial cell activity. Therefore, the present study investigates the effects of BoNT/A on a microglial murine cell lineage (BV-2) in different inflammatory conditions. Cellular viability and proliferation were carried out with different concentrations of BoNT/A (ranging from 0.3125 to 20 U/mL) for 24 h. Cells were primed with carrageenan (300 μg/mL) or Lipopolysaccharides (LPS) (20 ng/mL). The gene expression of IL-1β, IL-6, IL-18, TNF-α, Ikkβ, p65, Iba1 were quantified using PCR-RT. The supernatant was used to determine IL-1β, IL-6, and TNF-α levels. For all data, the significance level was set at 5%. Overall, data analysis revealed that BoNT/A 1.25 U/mL exhibited the greatest effect cell viability and proliferation. In addition, genes associated with inflammatory response in both stimuli (carrageenan and LPS) were downregulated in the presence of BoNT/A. Lastly, BoNT/A mitigates the protein levels of IL-1β and TNF-α in a time and dose-dependent manner. In conclusion, our results revealed that BoNT/A directly modulates the microglial cells' activities in an inflammatory context, opening new perspectives for using BoNT/A, considering its potential immunomodulatory effect.
期刊介绍：
Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee.
Toxicon''s "aims and scope" are to publish:
-articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms
-papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins
-molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins
-clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained.
-material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems.
-articles on the translational application of toxins, for example as drugs and insecticides
-epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged.
-articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon.
-review articles on problems related to toxinology.
To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.
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