Chronic Bronchitis Associated With Activation of MAPK Signaling in Alveolar Macrophages

Chronic Bronchitis Associated With Activation of MAPK Signaling in Alveolar Macrophages

shutterstock_53300002A new study entitled “Studies on mitogen-activated protein kinase signaling pathway in the alveolar macrophages of chronic bronchitis rats” shows that activated MAPK is a key step in chronic bronchitis and may thus be a potential new therapeutic target. The study was published in the journal Molecular and Cellular Biochemistry.

Chronic bronchitis, a lung disease leading to impaired airflow, is characterized by a continuous mucus-producing cough for a considered period of time as a result of inflammation in the bronchial tubes. The major risk group is smokers, however, workers exposed to industrial dusts and fumes, such as miners and metal workers are also at risk to develop the disease. With time, chronic bronchitis has a tendency to worsen, but people tend to only pay attention to the disease once it has already advanced which, at this stage, can be associated with lungs already being seriously injured.

Despite this, chronic bronchitis is usually manageable with early interventions. According to the American Lung Association, 9.9 million American were estimated to suffer from chronic bronchitis in 2009 alone.

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In this study, the authors aimed to further understand the chronic inflammation observed in chronic bronchitis, namely in its alveolar macrophages (those found in the pulmonary alveolus). Notably, the team had already found that in rat models for chronic bronchitis there was an increase of alveolar macrophages, and that these immune cells were a key factor for the development of chronic bronchitis due to its synthesis of inflammatory cytokines. A particular signaling pathway, the mitogen-activated protein kinases (MAPK), is known to be an important regulator of both alveolar macrophage proliferation and death. Thus, the authors looked how MAPK pathway impacts on alveolar macrophages profile in chronic bronchitis.

The authors induced chronic bronchitis in rats by injecting Bacillus Calmette Guerin intravenously, followed by LPS tracheal administration. They observed several players of the MAPK signaling pathway were activated in alveolar macrophages of chronic bronchitis rats. The authors further identified the two major signaling pathways regulating MAPK signaling in chronic bronchitis, by using different specific inhibitors. Specifically, the authors propose MAPK signaling in chronic bronchitis by two major cascades: the PTK-PI3K-Akt-JNK/p38 or PTK-PI3K- PKC-ERK.

These findings suggest that targeting MAPK signaling pathway may constitute a potential new therapeutic approach against chronic bronchitis.

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