Potential role of senescent macrophages in radiation-induced pulmonary fibrosis

Su, Lulu; Dong, Yinping; Wang, Yueying; Wang, Yuquan; Guan, Bowen; Lü, Yanhua; Wu, Jing; Wang, Xiaochun; Li, Deguan; Meng, Aimin; Fan, Feiyue

doi:10.1038/s41419-021-03811-8

Cited by 48 publications

(32 citation statements)

References 43 publications

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“…HNPC senescence was detected by the senescence-associated β-galactosidase (SA-β-Gal) staining kit. In senescent cells, a dark blue product was generated following the catalysis of senescence-specific β-galactosidase ( 26 ). TNF-α-induced HNPC senescence indicated a marked dark-blue color production, which was alleviated by treatment of the cells with different concentrations of luteolin ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Luteolin suppresses TNF‑α‑induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF‑κB pathway

et al. 2022

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Luteolin (3',4',5,7-tetrahydroxy flavone) is a flavonoid, which is widely distributed in various plants including flowers, vegetables, and medicinal herbs and spices. Luteolin can be applied in the treatment of various diseases due to its multiple biological activities, such as anti-inflammatory, anticancer, and antioxidative activity. However, its role in intervertebral disc degeneration has not been previously reported. Therefore, the purpose of the present study was to explore the effects of luteolin on Tumor necrosis factor (TNF)-α-induced inflammatory injury and senescence of human nucleus pulposus cells (HNPCs), as well as the underlying mechanisms of action of this compound. Cell viability and apoptosis were assessed by MTT assay and TUNEL staining, respectively. ELISA kits were applied to detect the levels of inflammatory cytokines and the activity of telomerase. Senescence β-galactosidase staining was used to detect the activity levels of β-galactosidase in the cells. Cell transfection was performed to achieve interference of sirtuin 6 (Sirt6). The protein expression levels were detected by western blot analysis. TUNEL staining and western blot analysis were performed to assess the expression levels of apoptosis-related proteins. The results indicated that TNF-α induced a significant decrease in HNPC viability and an increase in inflammatory factor levels, while the application of luteolin effectively increased cell viability and decreased intracellular interleukin (IL)-1β and IL-6 expression levels. Furthermore, luteolin decreased apoptosis compared with the TNF-α groups in a dose-dependent manner. In addition, the results of the detection kits suggested that luteolin reversed TNF-α-induced senescence. Notably, interference with Sirt6 partially reduced the protective effect of luteolin on TNF-α-induced HNPC senescence via the Sirt6/NF-κB pathway. In summary, the data indicated that luteolin suppresses TNF-α-induced inflammatory injury and senescence of HNPCs via the Sirt6/NF-κB pathway.

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Section: Resultsmentioning

confidence: 99%

Luteolin suppresses TNF‑α‑induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF‑κB pathway

et al. 2022

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“…Previous studies have shown that pulmonary macrophages play an important role in lung fibrosis and inflammatory response, which is usually a subsequent event of RP [ 39 ]. In the current study, we showed that the ratio of pulmonary macrophages raised slightly after irradiation ( Figure 2 c).…”

Section: Resultsmentioning

confidence: 99%

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

et al. 2022

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Radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), is a common clinical complication associated with thoracic radiotherapy for malignant tumors. However, the specific contributions of each cell subtype to this process are unknown. Here, we provide the single-cell pathology landscape of the RP in a mouse model by unbiased single-cell RNA-seq (scRNA-seq). We found a decline of type 2 alveolar cells in the RP lung tissue, with an expansion of macrophages, especially the Fabp4low and Spp1high subgroup, while Fabp4high macrophages were almost depleted. We observed an elevated expression of multiple mitochondrial genes in the RP group, indicating a type 2 alveolar cell (AT2) response to oxidative stress. We also calculated the enrichment of a cGAS-STING signaling pathway, which may be involved in regulating inflammatory responses and cancer progression in AT2 cells of PR mice. We delineate markers and transcriptional states, identify a type 2 alveolar cell, and uncover fundamental determinants of lung fibrosis and inflammatory response in RP lung tissue of mice.

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“…2c, pyrimethamine treatment markedly upregulated the percentages of SA-β-gal-positive cells. Senescent cells present a senescence-associated secretory phenotype (SASP) characterized by the increased expression of cytokines and chemokines such as IL-6, CCL2, CXCL1, and CXCL10 [12,13]. As shown in Fig.…”

Section: Pyrimethamine Induces Cellular Senescence Rather Than Apopto...mentioning

confidence: 99%

Pyrimethamine inhibits cell growth by inducing cell senescence and boosting CD8+ T-cell mediated cytotoxicity in colorectal cancer

Dong

et al. 2022

Mol Biol Rep

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Background The emergence of nonresponse or resistance to traditional chemotherapeutic agents is one of the main challenges of colorectal cancer (CRC) therapies. Thus, novel therapeutic drugs that can improve the clinical outcomes of CRC patients are urgently needed. The purpose of this study was to investigate the effects and mechanisms of pyrimethamine in CRC. Methods and results In this study, we assessed the role of pyrimethamine on CRC cell growth by cell counting kit-8 and colony formation assays. Cell cycle distribution and cellular senescence were determined by flow cytometry and senescence-associated β-galactosidase staining respectively. RNA-seq analysis and western blotting were used to investigate the potential pathways of pyrimethamine in CRC development. Moreover, animal experiments were performed to evaluate the effect of pyrimethamine in vivo. Our results demonstrated that pyrimethamine could inhibit cell growth by inducing S phase arrest followed by cellular senescence in CRC cells, and the p38MAPK-p53 axis was probably involved in that effect. In addition, pyrimethamine could also boost CD8+ T-cell mediated cytotoxicity and exert antitumor activity in vivo. Conclusion These results indicated that pyrimethamine may be a promising candidate agent for CRC treatment.

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Potential role of senescent macrophages in radiation-induced pulmonary fibrosis

Cited by 48 publications

References 43 publications

Luteolin suppresses TNF‑α‑induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF‑κB pathway

Luteolin suppresses TNF‑α‑induced inflammatory injury and senescence of nucleus pulposus cells via the Sirt6/NF‑κB pathway

Single-Cell Transcriptome Analysis of Radiation Pneumonitis Mice

Pyrimethamine inhibits cell growth by inducing cell senescence and boosting CD8+ T-cell mediated cytotoxicity in colorectal cancer

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