Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma
Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for...
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Frontiers Media S.A.
2018-09-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2018.01183/full |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Tabata M. dos Santos Renato F. Righetti Leandro do N. Camargo Beatriz M. Saraiva-Romanholo Beatriz M. Saraiva-Romanholo Luciana R. C. R. B. Aristoteles Flávia C. R. de Souza Silvia Fukuzaki Maria I. C. Alonso-Vale Maysa M. Cruz Carla M. Prado Carla M. Prado Edna A. Leick Milton A. Martins Iolanda F. L. C. Tibério |
spellingShingle |
Tabata M. dos Santos Renato F. Righetti Leandro do N. Camargo Beatriz M. Saraiva-Romanholo Beatriz M. Saraiva-Romanholo Luciana R. C. R. B. Aristoteles Flávia C. R. de Souza Silvia Fukuzaki Maria I. C. Alonso-Vale Maysa M. Cruz Carla M. Prado Carla M. Prado Edna A. Leick Milton A. Martins Iolanda F. L. C. Tibério Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma Frontiers in Physiology asthma interleukin-17 Rho-kinase Y-27632 inflammation neutralizing antibody |
author_facet |
Tabata M. dos Santos Renato F. Righetti Leandro do N. Camargo Beatriz M. Saraiva-Romanholo Beatriz M. Saraiva-Romanholo Luciana R. C. R. B. Aristoteles Flávia C. R. de Souza Silvia Fukuzaki Maria I. C. Alonso-Vale Maysa M. Cruz Carla M. Prado Carla M. Prado Edna A. Leick Milton A. Martins Iolanda F. L. C. Tibério |
author_sort |
Tabata M. dos Santos |
title |
Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma |
title_short |
Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma |
title_full |
Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma |
title_fullStr |
Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma |
title_full_unstemmed |
Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma |
title_sort |
effect of anti-il17 antibody treatment alone and in combination with rho-kinase inhibitor in a murine model of asthma |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2018-09-01 |
description |
Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease.Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation.Methods: Sixty-four BALBc mice, were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL17 (exposed-ovalbumin and anti-IL17); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 μg per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28).Results: Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4+, CD8+, ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-α, TGF-β, NF-κB, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF-β, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (p < 0.05).Conclusion: Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation. |
topic |
asthma interleukin-17 Rho-kinase Y-27632 inflammation neutralizing antibody |
url |
https://www.frontiersin.org/article/10.3389/fphys.2018.01183/full |
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doaj-8bd337a0f32e44998885c8952de539c52020-11-24T22:47:34ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-09-01910.3389/fphys.2018.01183398373Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of AsthmaTabata M. dos Santos0Renato F. Righetti1Leandro do N. Camargo2Beatriz M. Saraiva-Romanholo3Beatriz M. Saraiva-Romanholo4Luciana R. C. R. B. Aristoteles5Flávia C. R. de Souza6Silvia Fukuzaki7Maria I. C. Alonso-Vale8Maysa M. Cruz9Carla M. Prado10Carla M. Prado11Edna A. Leick12Milton A. Martins13Iolanda F. L. C. Tibério14Department of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Laboratory of Experimental Therapeutics, LIM-20, School of Medicine, University of São Paulo, São Paulo, BrazilDepartment of Medicine, University City of São Paulo (UNICID), São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Biological Sciences, Federal University of São Paulo, Diadema, BrazilDepartment of Biological Sciences, Federal University of São Paulo, Diadema, BrazilDepartment of Biological Sciences, Federal University of São Paulo, Diadema, BrazilDepartment of Biosciences, Federal University of São Paulo (UNIFESP), Santos, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilDepartment of Medicine, Faculdade de Medicina (FMUSP), Universidade de São Paulo, São Paulo, BrazilBackground: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease.Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation.Methods: Sixty-four BALBc mice, were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL17 (exposed-ovalbumin and anti-IL17); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 μg per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28).Results: Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4+, CD8+, ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-α, TGF-β, NF-κB, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF-β, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (p < 0.05).Conclusion: Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation.https://www.frontiersin.org/article/10.3389/fphys.2018.01183/fullasthmainterleukin-17Rho-kinaseY-27632inflammationneutralizing antibody |