Abstract
Background Pulmonary fibrosis is a chronic progressive fibrosis interstitial lung disease that is characterized by inflammatory infiltration and fibrotic changes. 5-Hydroxytryptamine (5-HT) is an important regulatory factor in inflammation, immunomodulation, and fibrosis. The aim of this study was to investigate the role of 5-HT in bleomycin- (BLM-) induced pulmonary fibrosis through wild-type C57BL/6 (WT) and TPH1 knockout (KO) mouse experiments. Methods The mice were grouped as follows: WT control group, KO control group, WT BLM group, and KO BLM group. Mice were administrated bleomycin hydrochloride through intratracheal instillation to induce pulmonary fibrosis. Mice were sacrificed 0, 7, 14, and 21 days after modeling, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected to determine the severity of fibrotic changes. Results The results showed that the weight loss of mice in the WT BLM group was more severe than that in the KO BLM group. H&E and Sirius Red staining revealed that 5-HT markedly aggravated histological damage and fibrotic changes in the lung. Significantly lower levels of hydroxyproline, Ashcroft fibrosis score, total BALF protein and cells, BALF tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6, TNF-α and IL-6 mRNA, malondialdehyde (MDA), and myeloperoxidase- (MPO-) positive cells in the lung tissues, and fibrosis-associated proteins were discovered in the mice from the KO BLM group compared with the WT BLM group. Conclusion 5-HT aggravated pulmonary fibrosis mainly by promoting the inflammation, exudation of proteins and cells, oxidative stress, and upregulation of fibrosis-associated genes in the lung tissues.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a type of progressive and irreversible chronic fibrotic interstitial lung disease with only 2–3-year survival once diagnosed [1]
The results showed that lower transcriptional levels of tumor necrosis factor- (TNF-)α and IL-6 were detected in KO BLM group mice in comparison to wild-type C57BL/6 (WT) BLM group mice (Figures 5(c) and 5(d))
Bleomycin is a classical antineoplastic drug that is commonly applied for pulmonary fibrosis modeling in rodents
Summary
Idiopathic pulmonary fibrosis (IPF) is a type of progressive and irreversible chronic fibrotic interstitial lung disease with only 2–3-year survival once diagnosed [1]. Pulmonary fibrosis is a chronic progressive fibrosis interstitial lung disease that is characterized by inflammatory infiltration and fibrotic changes. Lower levels of hydroxyproline, Ashcroft fibrosis score, total BALF protein and cells, BALF tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6, TNF-α and IL-6 mRNA, malondialdehyde (MDA), and myeloperoxidase- (MPO-) positive cells in the lung tissues, and fibrosis-associated proteins were discovered in the mice from the KO BLM group compared with the WT BLM group. 5-HT aggravated pulmonary fibrosis mainly by promoting the inflammation, exudation of proteins and cells, oxidative stress, and upregulation of fibrosis-associated genes in the lung tissues Conclusion. 5-HT aggravated pulmonary fibrosis mainly by promoting the inflammation, exudation of proteins and cells, oxidative stress, and upregulation of fibrosis-associated genes in the lung tissues
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