Serotonin Exhibits Accelerated Bleomycin-Induced Pulmonary Fibrosis through TPH1 Knockout Mouse Experiments

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.

Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis

“…Moreover, bleomycin instillation binds molecular oxygen and Fe (II), producing ROS mediators and causing lipid peroxidation [ 47 ]. Adelmidrol treatment reduced the significant disability of antioxidants and elevation of the oxidant burden, as shown by the SOD activity and MDA and GSH levels, induced by bleomycin instillation [ 28 , 31 , 48 ]. Mice subjected to an experimental model of pulmonary fibrosis showed NO over-production [ 49 , 50 , 51 ], similar to patients affected by this pathology [ 52 ].…”

“…The bronchoalveolar fluid lavage (BALF) IL,6 IL-1β, TNF-α, and TGF-1β levels were detected by using ELISA kits (Dakewe, Shenzhen, China; Biosource International, Camarillo, CA) [ 28 , 29 , 30 ]. Levels of IL6 IL-1β, TNF-α, and TGF-1β in lung tissues were measured by using ELISA kits (Calbiochem-Novabiochem Corporation, USA) [ 31 , 32 ].…”

“…The malondialdehyde (MDA) [ 34 ], glutathione (GSH), and SOD levels in the lung tissues were measured using activity assay kits (Nanjing Jiancheng Bioengineering Institute) [ 28 ].…”

Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor as a Novel Therapeutic Tool for Lung Injury

“…The bronchoalveolar fluid lavage (BALF) IL,6 IL-1β, TNF-α and TGF-β levels were detected by using ELISA kits (Dakewe, Shenzhen, China; Biosource International, Camarillo, CA, USA; R&D, Minneapolis, MN, USA) [ 40 , 41 , 42 ]. Levels of IL6 IL-1β and TNF-α in lung tissues were measured by using ELISA kits (Calbiochem-Novabiochem Corporation, San Diego, CA, USA) [ 43 , 44 ].…”

“…The malondialdehyde (MDA) [ 46 ], glutathione (GSH) and superoxide dismutase (SOD) levels in the lung tissues were measured using activity assay kits (Nanjing Jiancheng Bioengineering Institute, Jiangsu, China) [ 40 ].…”