Different profiles of notch signaling in cigarette smoke-induced pulmonary emphysema and bleomycin-induced pulmonary fibrosis
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Different profiles of Notch signaling mediate naive T cell differentiation which might be involved in pulmonary emphysema and fibrosis.
C57BL/6 mice were randomized into cigarette smoke (CS) exposure, bleomycin (BLM) exposure, and two separate groups of control for sham exposure to CS or BLM. The paratracheal lymph nodes of the animals were analyzed by real-time PCR and immunohistochemistry. Morphometry of the lung parenchyma, measurement of the cytokines, and cytometry of the bronchoalveolar lavage fluid (BALF) were also done accordingly.
In comparison with controls, all Notch receptors and ligands were upregulated by chronic CS exposure, especially Notch3 and DLL1 (P < 0.01), and this was in line with emphysema-like morphology and Th1-biased inflammation. While Notch3 and DLL1 were downregulated by BLM exposure (P < 0.01), those was in line with fibrotic lung remodeling and Th2 polarization.
This founding implies that the CS exposure but not the BLM exposure is capable of initiating Notch signaling in lymphoid tissue of the lung, which is likely relevant to the pathogenesis of pulmonary emphysema. Unable to initiate the Th1 response or inhibit it may lead to Th2 polarization and aberrant repair.
KeywordsNotch Th1/Th2 response Pulmonary emphysema Pulmonary fibrosis
Excessive extracellular matrix
Bronchoalveolar lavage fluid
Mean linear intercept
Internal surface area
Chronic obstructive pulmonary disease
This research is supported by the science foundation of Hubei Province, China (Grant No.2008CDB153). The authors thank Dr. Chen Yaobin and Dr. Xia Qin for their technique assistance.
Conflict of interest
The authors declare that they have no conflict of interest.
The protocols for the animal experiments were approved by Tongji Medical College, Huazhong University of Science and Technology, and Hubei Laboratory Animal Society (Wuhan, China).
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