Pirfenidone is a representative medication to treat interstitial pulmonary fibrosis. Researchers reported pirfenidone (>100 µg/ml) significantly suppressed fibroblast growth . However, clinically, the maximum concentration of pirfenidone in the blood is approximately 10 µg/ml. We hypothesized there might be an additional mechanism of pirfenidone to fibroblasts indirectly. Macrophages are known to control the activation of fibroblasts via the regulation of inflammatory M1 and suppressive M2 polarization. The aim of this study was to investigate the effects of pirfenidone on alveolar macrophage polarization. Rat alveolar macrophages (NR8383) were stimulated with lipopolysaccharide (LPS) + interferon (IFN)-γ, or interleukin (IL)-4 + IL-13. Expression of M1 and M2 markers and supernatant's levels of TGF-β1 were assessed after pirfenidone treatment (0-100 µg/ml). Treatment with LPS + INF-γ or IL-4 + IL-13 significantly increased the expression of M1 and M2 markers, respectively. In macrophage polarization assays, pirfenidone significantly reduced the expression of M2 markers at concentrations greater than 10 µg/ml but had no effect on the expression of M1 markers. At these concentrations, pirfenidone significantly reduced TGF-β1 levels in NR8383 culture supernatants. In rat lung fibroblasts treated with NR8383 culture supernatants, pirfenidone significantly suppressed proliferation, and the collagen mRNA and protein levels. In conclusion, our results demonstrated that pirfenidone suppressed polarization to M2 macrophages at clinically relevant concentrations and suppressed the rat lung fibroblasts fibrogenic activity.
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http://dx.doi.org/10.3164/jcbn.17-111 | DOI Listing |
Discov Oncol
December 2024
School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, People's Republic of China.
Objective: Searching for potential biomarkers and therapeutic targets for early diagnosis of gynecological tumors to improve patient survival.
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Mol Neurobiol
December 2024
NHC Key Laboratory of Drug Addiction Medicine, School of Forensic Medicine, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue Chenggong District, Kunming, 650500, China.
Co-exposure to methamphetamine (METH) abuse and HIV infection exacerbates central nervous system damage. However, the underlying mechanisms of this process remain poorly understood. This study aims to explore the roles of neuronal autophagy in the synergistic damage to the central nervous system caused by METH and HIV proteins.
View Article and Find Full Text PDFBiochem Genet
December 2024
Botany and Microbiology Department, Faculty of Science, Helwan University, Ain Helwan, Cairo, 11795, Egypt.
Pearl millet {Pennisetum glaucum (L.) R. Br} is a C4 panicoid cereal millet crop grown in arid and semi-arid regions in Africa and Asia for food and fodder.
View Article and Find Full Text PDFElife
December 2024
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Parkinson's disease (PD) is a multifactorial disease caused by irreversible progressive loss of dopaminergic neurons (DANs). Recent studies have reported the successful conversion of astrocytes into DANs by repressing polypyrimidine tract binding protein 1 (PTBP1), which led to the rescue of motor symptoms in a chemically-induced mouse model of PD. However, follow-up studies have questioned the validity of this astrocyte-to-DAN conversion model.
View Article and Find Full Text PDFFASEB J
December 2024
Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Saitama, Japan.
Flavan-3-ols (FL) are poorly bioavailable astringent polyphenols that induce hyperactivation of the sympathetic nervous system. The aim of this study was to investigate the effects of repeated oral administration of FL on mice hindlimb skeletal muscle using immunohistochemical techniques. C57BL/6J male mice were orally administered 50 mg/kg of FL for a period of 2 weeks, and bromideoxyuridine (BrdU) was administered intraperitoneally 3 days prior to the dissection.
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