methods-for-detecting-cough-and-airway-inflammation-in-mice

Methods for Detecting Cough and Airway Inflammation in Mice

Chronic cough, which lasts for more than 8 weeks, is one of the most common complaints requiring medical attention, and patients suffer from a huge ...

The First Affiliated Hospital of Guangzhou Medical University

Respiratory viral infection increases the number of lung-resident T lymphocytes, which enhance cough sensitivity by producing interferon-γ (IFN-γ). It is poorly understood why IFN-γ-secreting T lymphocytes persist for a long time when the respiratory viruses have been removed.

Pulmonary IFN-γ Causes Lymphocytic Inflammation and Cough Hypersensitivity by Increasing the Number of IFN-γ-Secreting T Lymphocytes.

Not all gastroesophageal reflux-induced cough (GERC) patients respond to anti-reflux treatment. It is not certain whether reflux-related symptoms or other clinical characteristics could indicate a successful response to anti-reflux treatment. In this study, we aimed to investigate the relationship between clinical features and anti-reflux response.

Predictive value of clinical features for anti-reflux therapy response in suspected gastroesophageal reflux-induced chronic cough.

Some patients with chronic refractory cough have high levels of pulmonary IFN-γ and IFN-γ-producing T lymphocytes. Pulmonary IFN-γ administration causes acute airway lymphocytic inflammation and cough hypersensitivity by increasing the number of pulmonary IFN-γ-producing T lymphocytes, but these lymphocytes may be recruited from other organs. Intraperitoneal IFN-γ injection can increase the spleen weight of mice. It remains elusive whether pulmonary IFN-γ can induce chronic airway lymphocytic inflammation and cough hypersensitivity by stimulating the proliferation of IFN-γ -producing T lymphocytes in the spleen. Here, we found that pulmonary IFN-γ administration induced chronic airway inflammation and chronic cough hypersensitivity with an increased number of IFN-γ-producing T lymphocytes in the spleen, blood and lung. Pulmonary IFN-γ administration also increased 1) the proliferation of spleen lymphocytes in vivo and 2) the IP-10 level and CXCR3 T lymphocyte numbers in the spleen and lung of mice. IP-10 could promote the proliferation of spleen lymphocytes in vitro but not blood lymphocytes or lung-resident lymphocytes. AMG487, a potent inhibitor of binding between IP-10 and CXCR3, could block pulmonary IFN-γ instillation-induced chronic airway lymphocytic inflammation and the proliferation of IFN-γ-producing T lymphocytes in mouse spleens. In conclusion, intrapulmonary IFN-γ instillation may induce the proliferation of splenic IFN-γ-producing T lymphocytes through IP-10 and the CXCR3 pathway. The IFN-γ-producing T lymphocytes in blood, partly released from the mouse spleen, may be partly attracted to the lung by pulmonary IP-10 through the CXCR3 pathway. IFN-γ-producing T lymphocytes and IFN-γ in the lung may cause chronic airway lymphocytic inflammation and chronic cough hypersensitivity.

Intrapulmonary IFN-γ instillation causes chronic lymphocytic inflammation in the spleen and lung through the CXCR3 pathway.

Eosinophilic asthma (EA) and non-asthmatic eosinophilic bronchitis (EB) share similar eosinophilic airway inflammation. Unlike EA, EB did not present airway hyperresponsiveness or airflow obstruction. We aimed to compare the mechanism underlying the different manifestations between EA and EB via sputum transcriptomics analysis.

Sputum Transcriptomics Reveals FCN1+ Macrophage Activation in Mild Eosinophilic Asthma Compared to Non-Asthmatic Eosinophilic Bronchitis.

Severe influenza virus-infected patients have high systemic levels of Th1 cytokines (including IFN-γ). Intrapulmonary IFN-γ increases pulmonary IFN-γ-producing T lymphocytes through the CXCR3 pathway. Virus-infected mice lacking IP-10/CXCR3 demonstrate lower pulmonary neutrophilic inflammation. AMG487, an IP-10/CXCR3 antagonist, ameliorates virus-induced lung injury in vivo through decreasing viral loads. This study examined whether AMG487 could treat H1N1 virus-induced mouse illness through reducing viral loads or decreasing the number of lymphocytes or neutrophils.

Wenbin Ding

State Key Laboratory of Respiratory Disease,
Guangzhou Institute of Respiratory Health,
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health

The First Affiliated Hospital of Guangzhou Medical University

Methods for Detecting Cough and Airway Inflammation in Mice

Wenbin Ding

State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Health,State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health

The First Affiliated Hospital of Guangzhou Medical University

Methods for Detecting Cough and Airway Inflammation in Mice

State Key Laboratory of Respiratory Disease,
Guangzhou Institute of Respiratory Health,
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health