Instituto de Ciencias Biomédicas (ICB), Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910132, Chile.
Int J Mol Sci. 2024 Mar 9;25(6):3150. doi: 10.3390/ijms25063150.
Inflammation and mucus production are prevalent characteristics of chronic respiratory conditions, such as asthma and chronic chronic obstructive pulmonary disease (COPD). Biological co-factors, including bacteria, viruses, and fungi, may exacerbate these diseases by activating various pathways associated with airway diseases. An example is the fungus , which is linked to severe COPD in human patients. Recent evidence has demonstrated that significantly enhanced inflammation and mucus hypersecretion in a rat model of elastase-induced COPD. The present study specifically aims to investigate two additional aspects associated with the pathology induced by infection: inflammation and collagen deposition around airways. To this end, the focus was to investigate the role of the IL-1β pro-inflammatory pathway during infection in COPD rats. Several airway pathology-related features, such as inflammation, mucus hypersecretion, and fibrosis, were evaluated using histological and molecular techniques. COPD animals infected with exhibited elevated inflammation levels, including a synergistic increase in IL-1β and Cox-2. Furthermore, protein levels of the IL-1β-dependent transcription factor cAMP response element-binding (CREB) showed a synergistic elevation of their phosphorylated version in the lungs of COPD animals infected with , while mucus levels were notably higher in the airways of COPD-infected animals. Interestingly, a CREB responsive element (CRE) was identified in the Muc5b promoter. The presence of CREB in the Muc5b promoter was synergistically increased in COPD animals infected with compared to other experimental groups. Finally, an increment of deposited collagen was identified surrounding the airways of COPD animals infected with compared with the other experimental animal groups and correlated with the increase of mRNA levels. These findings emphasize the role of as a potential biological co-factor in chronic respiratory diseases like COPD or asthma, warranting new perspectives in the treatment of chronic respiratory diseases.
炎症和黏液产生是慢性呼吸道疾病（如哮喘和慢性阻塞性肺疾病（COPD））的常见特征。生物共因子，包括细菌、病毒和真菌，可能通过激活与气道疾病相关的各种途径来加重这些疾病。例如，真菌与人类严重 COPD 有关。最近的证据表明，在弹性蛋白酶诱导的 COPD 大鼠模型中，显著增强了炎症和黏液分泌亢进。本研究特别旨在研究与 感染相关的病理学的另外两个方面：气道周围的炎症和胶原沉积。为此，重点研究了 IL-1β 促炎途径在 COPD 大鼠 感染中的作用。使用组织学和分子技术评估了与气道病理学相关的几个特征，如炎症、黏液分泌亢进和纤维化。感染 的 COPD 动物表现出炎症水平升高，包括 IL-1β 和 Cox-2 的协同增加。此外，IL-1β 依赖性转录因子 cAMP 反应元件结合（CREB）的蛋白水平在感染 的 COPD 动物肺部显示出其磷酸化形式的协同升高，而 COPD 感染动物的气道中的黏液水平明显更高。有趣的是，在 Muc5b 启动子中鉴定出了 CREB 反应元件（CRE）。与其他实验组相比，感染 的 COPD 动物中 Muc5b 启动子中的 CREB 协同增加。最后，在感染 的 COPD 动物的气道周围鉴定出沉积的胶原增加，与其他实验组相比，与 mRNA 水平的增加相关。这些发现强调了 作为 COPD 或哮喘等慢性呼吸道疾病的潜在生物共因子的作用，为慢性呼吸道疾病的治疗提供了新的视角。
