Effects of plant protease inhibitors (Pep-3-EcTI, Pep-BbKI, and Pep-BrTI) versus corticosteroids on inflammation, remodeling, and oxidative stress in an asthma-COPD (ACO) model.

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.

Effects of environmental exposure to iron powder on healthy and elastase-exposed mice.

Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1ß, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-ß, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes.

Alpha-7 Nicotinic Receptor Agonist Protects Mice Against Pulmonary Emphysema Induced by Elastase.

Pulmonary emphysema is a primary component of chronic obstructive pulmonary disease (COPD), a life-threatening disorder characterized by lung inflammation and restricted airflow, primarily resulting from the destruction of small airways and alveolar walls. Cumulative evidence suggests that nicotinic receptors, especially the α7 subtype (α7nAChR), is required for anti-inflammatory cholinergic responses. We postulated that the stimulation of α7nAChR could offer therapeutic benefits in the context of pulmonary emphysema. To investigate this, we assessed the potential protective effects of PNU-282987, a selective α7nAChR agonist, using an experimental emphysema model. Male mice (C57BL/6) were submitted to a nasal instillation of porcine pancreatic elastase (PPE) (50 µl, 0.667 IU) to induce emphysema. Treatment with PNU-282987 (2.0 mg/kg, ip) was performed pre and post-emphysema induction by measuring anti-inflammatory effects (inflammatory cells, cytokines) as well as anti-remodeling and anti-oxidant effects. Elastase-induced emphysema led to an increase in the number of α7nAChR-positive cells in the lungs. Notably, both groups treated with PNU-282987 (prior to and following emphysema induction) exhibited a significant decrease in the number of α7nAChR-positive cells. Furthermore, both groups treated with PNU-282987 demonstrated decreased levels of macrophages, IL-6, IL-1ß, collagen, and elastic fiber deposition. Additionally, both groups exhibited reduced STAT3 phosphorylation and lower levels of SOCS3. Of particular note, in the post-treated group, PNU-282987 successfully attenuated alveolar enlargement, decreased IL-17 and TNF-α levels, and reduced the recruitment of polymorphonuclear cells to the lung parenchyma. Significantly, it is worth noting that MLA, an antagonist of α7nAChR, counteracted the protective effects of PNU-282987 in relation to certain crucial inflammatory parameters. In summary, these findings unequivocally demonstrate the protective abilities of α7nAChR against elastase-induced emphysema, strongly supporting α7nAChR as a pivotal therapeutic target for ameliorating pulmonary emphysema.

Modulating asthma-COPD overlap responses with IL-17 inhibition.

Background: IL-17 is a modulator of the inflammatory response and is implicated in lung remodeling in both asthma and chronic obstructive pulmonary disease (COPD). Well as and probably in patients with asthma-COPD overlap (ACO). Methods: In this study, we evaluated the response of the airways and alveolar septa to anti-IL-17 treatment in an ACO model. Fifty-six male BALB/c mice were sensitized with ovalbumin (OVA group), received porcine pancreatic elastase (PPE group), or both (ACO group). Mice were then treated with either anti-IL-17 monoclonal antibody or saline. We evaluated hyperresponsiveness, bronchoalveolar lavage fluid (BALF) cell counts, and mean alveolar diameter. We quantified inflammatory, response, extracellular matrix remodeling, oxidative stress markers, and signaling pathway markers. Results: Anti-IL-17 treatment in the ACO anti-IL-17 group reduced the maximum response of respiratory system Rrs, Ers, Raw, Gtis, this when compared to the ACO group (p<0.05). There was a reduction in the total number of inflammatory cells, neutrophils, and macrophages in the BALF in the ACO anti-IL-17 group compared to the ACO group (p<0.05). There was attenuated dendritic cells, CD4+, CD8+, FOXP3, IL-1ß, IL-2, IL-6, IL-13, IL-17, IL-33 in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p<0.05). We observed a reduction of MMP-9, MMP-12, TIMP-1, TGF-ß, collagen type I in ACO anti-IL-17 group in airway and alveolar septum compared to the ACO group (p < 0.05). We also observed a reduction of iNOS and 8-iso-PGF2α in the airways and in the alveolar septum was reduced in the ACO anti-IL-17group compared to the ACO group (p < 0.05). Regarding the signaling pathways, NF-kB, ROCK-1, and ROCK-2 in the airway and alveolar septum were attenuated in the ACO anti-IL-17 group when compared to the ACO group (p<0.05). Conclusions: Our results suggest that inhibiting IL-17 modulates cell-associated cytokine production in lung tissue, extracellular matrix remodeling, and oxidative stress in ACO through the modulation of NF-kB and FOXP3.

Investigating the Effects of a New Peptide, Derived from the Enterolobium contortisiliquum Proteinase Inhibitor (EcTI), on Inflammation, Remodeling, and Oxidative Stress in an Experimental Mouse Model of Asthma-Chronic Obstructive Pulmonary Disease Overlap (ACO).

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-ß), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-ß, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1ß, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-ß, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.

Effects of a Peptide Derived from the Primary Sequence of a Kallikrein Inhibitor Isolated from Bauhinia bauhinioides (pep-BbKI) in an Asthma-COPD Overlap (ACO) Model.

(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-ß, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO (p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1ß(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-ß (AS), collagen fibers (AW), iNOS, and eNO (p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons (p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.

Preventive and therapeutic effect of anti-IL-17 in an experimental model of elastase-induced lung injury in C57Bl6 mice.

Chronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-кB, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-ß, tumor necrosis factor-α, neutrophils, IL-1ß, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.

Effect of anti-IL17 and/or Rho-kinase inhibitor treatments on vascular remodeling induced by chronic allergic pulmonary inflammation.

BACKGROUND AND AIMS: Expansion and morphological dysregulation of the bronchial vascular network occurs in asthmatic airways. Interleukin (IL) -17 and Rho-kinase (ROCK) are known to act in inflammation control and remodeling. Modulation of Rho-kinase proteins and IL-17 may be a promising approach for the treatment of asthma through the control of angiogenesis. Our objective was to analyze the effects of treatment with anti-IL17 and/or Rho-kinase inhibitor on vascular changes in mice with chronic allergic pulmonary inflammation. METHODS: Sixty-four BALB/c mice, with pulmonary inflammation induced by ovalbumin were treated with anti-IL17A (7.5/µg per dose, intraperitoneal) and/or Rho-kinase inhibitor (Y-27632-10 mg/kg, intranasal), 1 h before each ovalbumin challenge (22, 24, 26, and 28/days). Control animals were made to inhale saline. At the end of the protocol, lungs were removed, and morphometric analysis was performed to quantify vascular inflammatory, remodeling, and oxidative stress responses. RESULTS: Anti-IL17 or Rho-kinase inhibitor reduced the number of CD4+, CD8+, dendritic cells, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, Rho-kinase 1 and 2, transforming growth factor (TGF-ß), vascular endothelial growth factor (VEGF), nuclear factor (NF)-KappaB, iNOS, metalloproteinase (MMP)-9, MMP-12, metalloproteinase inhibitor-1 (TIMP-1), FOXP-3, signal transducer and activator of transcription 1 (STAT1) and phospho-STAT1-positive cells, and actin, endothelin-1, isoprostane, biglycan, decorin, fibronectin and the collagen fibers volume fraction compared with the ovalbumin group (p < 0.05). The combination treatment, when compared with anti-IL17, resulted in potentiation of decrease in the number of IL1ß- and dendritic cells-positive cells. When we compared the OVA-RHO inhibitor-anti-IL17 with OVA-RHO inhibitor we found a reduction in the number of CD8+ and IL-17, TGF-ß, and phospho-STAT1-positive cells and endothelin-1 in the vessels (p < 0.05). There was an attenuation in the number of ROCK 2-positive cells in the group with the combined treatment when compared with anti-IL17 or Rho-kinase inhibitor-treated groups (p < 0.05). CONCLUSION: We observed no difference in angiogenesis after treatment with Rho-kinase inhibitor and anti-IL17. Although the treatments did not show differences in angiogenesis, they showed differences in the markers involved in the angiogenesis process contributing to inflammation control and vascular remodeling.The reviews of this paper are available via the supplemental material section.

Bronchial Vascular Remodeling Is Attenuated by Anti-IL-17 in Asthmatic Responses Exacerbated by LPS.

INTRODUCTION: Although the major alterations associated with asthma are related to the airways, there is also evidence of the importance of peribronchial vascular inflammation and remodeling in its pathophysiology. OBJECTIVES: To determine the effects of anti-IL-17 therapy on peribronchial vessels of an asthma model exacerbated by lipopolysaccharide. METHODS: We evaluated several factors, including lung function, inflammation, oxidative stress, vascular remodeling, and signaling pathways present in the peribronchial vessels of 66 male BALB/c mice exposed to ovalbumin and treated (or not) treated with anti-IL-17. Twenty-four hours before the end of the experimental protocol, groups of sensitized animals (OVA-LPS and OVA-LPS anti-IL-17) also received LPS. RESULTS: The OVA-LPS-anti-IL-17 group presented a decrease in several factors [airway resistance and elastance, bronchoalveolar lavage fluid (BALF) cell counts, inflammatory response, eosinophils, TSLP, IL-33, TARC, TNF-α, CD4+, CD8+, IL-4, IL-6, IL-10, IL-17, and VEGF positive cells/104µm2, peribronchovascular edema, and angiogenesis], including remodeling (MMP-9, MMP-12, TIMP-1 and TGF-ß positive cells and volume fraction of collagen fibers I, collagen fibers III, collagen fibers V, decorin, lumican, actin, biglycan, fibronectin, and integrin), oxidative stress (iNOS positive cells and volume fraction of PGF2α), and signaling pathways (FoxP3), as well as dendritic cells, NF-kB, ROCK-1, ROCK-2, STAT-1, and phosphor-STAT1-positive cells compared to OVA-LPS (p < 0.05). CONCLUSIONS: In this model of LPS-induced asthma exacerbation, IL-17 inhibition represents a promising therapeutic strategy, indicating the potential of bronchial vascular control of Th2 and Th17 responses and the activation of the remodeling and oxidative stress pathways, associated with the control of signaling pathways.

Protective Effects of Anti-IL17 on Acute Lung Injury Induced by LPS in Mice.

Introduction: T helper 17 (Th17) has been implicated in a variety of inflammatory lung and immune system diseases. However, little is known about the expression and biological role of IL-17 in acute lung injury (ALI). We investigated the mechanisms involved in the effect of anti-IL17 in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods: Mice were pre-treated with anti-IL17, 1h before saline/LPS intratracheal administration alongside non-treated controls and levels of exhaled nitric oxide (eNO), cytokine expression, extracellular matrix remodeling and oxidative stress, as well as immune cell counts in bronchoalveolar lavage fluid (BALF), and respiratory mechanics were assessed in lung tissue. Results: LPS instillation led to an increase in multiple cytokines, proteases, nuclear factor-κB, and Forkhead box P3 (FOXP3), eNO and regulators of the actomyosin cytoskeleton, the number of CD4+ and iNOS-positive cells as well as the number of neutrophils and macrophages in BALF, resistance and elastance of the respiratory system, ARG-1 gene expression, collagen fibers, and actin and 8-iso-PGF2α volume fractions. Pre-treatment with anti-IL17 led to a significant reduction in the level of all assessed factors. Conclusions: Anti-IL17 can protect the lungs from the inflammatory effects of LPS-induced ALI, primarily mediated by the reduced expression of cytokines and oxidative stress. This suggests that further studies using anti-IL17 in a treatment regime would be highly worthwhile.

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 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-ß, 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-ß, 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.

Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS.

Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-κB, and Rho kinase 1- and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.