Different profiles of notch signaling in cigarette smoke-induced pulmonary emphysema and bleomycin-induced pulmonary fibrosis.

Abstract

OBJECTIVE:

Different profiles of Notch signaling mediate naive T cell differentiation which might be involved in pulmonary emphysema and fibrosis.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Shi Li, Xiaofei Hu, Zheng Wang, Meng Wu, Jinnong Zhang
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 64 Issue 5 Pg. 363-71 (May 2015) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 25813392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Receptors, Notch
• Smoke
• Bleomycin
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Antimetabolites, Antineoplastic
• Bleomycin
• Bronchoalveolar Lavage Fluid (cytology)
• Gene Expression Regulation (drug effects)
• Interferon-gamma (metabolism)
• Interleukin-4 (metabolism)
• Lung (pathology)
• Lymph Nodes (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Pulmonary Emphysema (chemically induced, pathology)
• Pulmonary Fibrosis (chemically induced, pathology)
• Receptors, Notch (drug effects)
• Signal Transduction (drug effects)
• Smoke (adverse effects)
• Tobacco