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Abstract：
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).
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.
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-1β, 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-β, 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).
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.
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.
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-1β, 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-β, 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).
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.
摘要：
IL-17是炎症反应的调节剂,并且与哮喘和慢性阻塞性肺病(COPD)的肺重塑有关。以及可能在哮喘-COPD重叠（ACO）患者中。
■在这项研究中，我们在ACO模型中评估了气道和肺泡间隔对抗IL-17治疗的反应.56只雄性BALB/c小鼠用卵清蛋白致敏（OVA组），接受猪胰弹性蛋白酶（PPE组），或两者(ACO组)。然后用抗IL-17单克隆抗体或盐水处理小鼠。我们评估了高反应性，支气管肺泡灌洗液（BALF）细胞计数，和平均肺泡直径。我们量化了炎症，回应,细胞外基质重塑，氧化应激标志物，和信号通路标记。
■ACO抗IL-17组的抗IL-17治疗降低了呼吸系统Rrs的最大反应，ERS,Raw,Gtis,与ACO组相比（p<0.05）。炎症细胞总数减少，中性粒细胞，与ACO组相比,ACO抗IL-17组的BALF中的巨噬细胞(p<0.05)。有减毒的树突状细胞,CD4+,CD8+,FOXP3,IL-1β,IL-2、IL-6、IL-13、IL-17、IL-33在ACO抗IL-17组的气道和肺泡隔与ACO组比拟(p<0.05)。我们观察到MMP-9，MMP-12，TIMP-1，TGF-β，ACO抗IL-17组I型胶原在气道和肺泡隔的表达与ACO组比较(p<0.05)。我们还观察到，与ACO组相比，ACO抗IL-17组的气道和肺泡隔中iNOS和8-iso-PGF2α的减少（p<0.05）。关于信号通路，NF-kB,与ACO组相比，ACO抗IL-17组的气道和肺泡隔膜中的ROCK-1和ROCK-2减弱（p<0.05）。
■我们的结果表明，抑制IL-17可调节肺组织中细胞相关细胞因子的产生，细胞外基质重塑，通过调节NF-kB和FOXP3在ACO中的氧化应激。
■在这项研究中，我们在ACO模型中评估了气道和肺泡间隔对抗IL-17治疗的反应.56只雄性BALB/c小鼠用卵清蛋白致敏（OVA组），接受猪胰弹性蛋白酶（PPE组），或两者(ACO组)。然后用抗IL-17单克隆抗体或盐水处理小鼠。我们评估了高反应性，支气管肺泡灌洗液（BALF）细胞计数，和平均肺泡直径。我们量化了炎症，回应,细胞外基质重塑，氧化应激标志物，和信号通路标记。
■ACO抗IL-17组的抗IL-17治疗降低了呼吸系统Rrs的最大反应，ERS,Raw,Gtis,与ACO组相比（p<0.05）。炎症细胞总数减少，中性粒细胞，与ACO组相比,ACO抗IL-17组的BALF中的巨噬细胞(p<0.05)。有减毒的树突状细胞,CD4+,CD8+,FOXP3,IL-1β,IL-2、IL-6、IL-13、IL-17、IL-33在ACO抗IL-17组的气道和肺泡隔与ACO组比拟(p<0.05)。我们观察到MMP-9，MMP-12，TIMP-1，TGF-β，ACO抗IL-17组I型胶原在气道和肺泡隔的表达与ACO组比较(p<0.05)。我们还观察到，与ACO组相比，ACO抗IL-17组的气道和肺泡隔中iNOS和8-iso-PGF2α的减少（p<0.05）。关于信号通路，NF-kB,与ACO组相比，ACO抗IL-17组的气道和肺泡隔膜中的ROCK-1和ROCK-2减弱（p<0.05）。
■我们的结果表明，抑制IL-17可调节肺组织中细胞相关细胞因子的产生，细胞外基质重塑，通过调节NF-kB和FOXP3在ACO中的氧化应激。
