Triptolide mitigates radiation-induced pulmonary fibrosis via inhibition of axis of alveolar macrophages-NOXes-ROS-myofibroblasts

Chen, Chun; Yang, Shanmin; Zhang, Mei; Zhang, Zhenhuan; Hong, Jingshen; Han, Deping; Ma, Jun; Zhang, Steven B.; Okunieff, Paul; Zhang, Lurong

doi:10.1080/15384047.2016.1139229

Cited by 32 publications

(23 citation statements)

References 37 publications

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“…ROS can promote the expression of plasminogen activator inhibitor‐1 (PAI‐1), and overexpression of PAI‐1 can lead to excessive accumulation of collagen in damaged lung tissue. Extracellular matrix (ECM) cannot degrade and eventually leads to the formation of pulmonary fibrosis . At present, normal antioxidants used in clinics are not effective in the treatment of pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…NOX2 has been reported to be a major source of ROS with pulmonary inflammation. The anti‐fibrotic effect of triptolide on IR‐induced pulmonary fibrosis was associated with its inhibition on the axis of alveolar macrophages‐NOXes‐ROS‐myofibroblasts . NOX4 plays an important role in the pathological process of acute lung injury to fibrosis .…”

Section: Discussionmentioning

confidence: 99%

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Mechanisms involved in inflammatory pulmonary fibrosis induced by lunar dust simulant in rats

Sun

Liu

Zhang

et al. 2018

Environmental Toxicology

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Lunar dust is one of the biggest risk factors in the future manned exploration mission. Much is not known about the pulmonary toxicity of lunar dust. The aim of this study was to evaluate the lung inflammation and oxidative stress induced by subacute exposure to lunar dust stimulant (LDS) in rats. Wistar rats were intratracheally administered LDS, twice a week for 3 weeks. Inflammatory cell counting and cytokine assays using bronchoalveolar lavage fluid (BALF) were performed. Lung tissues were processed for histopathological examination and immunohistochemical staining. Biomarkers of oxidative stress and genes and proteins related to inflammation and fibrosis in lung tissue were also determined. The neutrophil count in the BALF of LDS‐exposed groups was higher than that in controls (P < .05). LDS caused a significant increase in some of biochemical indicators and proinflammatory factors levels in BALF compared with control group. The normal balance between oxidation and antioxidation was broken by LDS. Pathological characteristics of lung tissue and immunohistochemical results for α‐smooth muscle actin (α‐SMA) indicated that inflammatory response was an extremely important passage to pulmonary fibrosis. Real‐time PCR analysis showed elevated levels of nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) mRNA in the lungs (P < .05). Western blotting results were consistent with immunohistochemistry and qPCR results. These results indicate that inhalation of lunar dust may cause inflammatory pulmonary fibrosis. NOX4 may be a key potential therapeutic target for inflammatory injury and fibrosis in the lung.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanisms involved in inflammatory pulmonary fibrosis induced by lunar dust simulant in rats

Sun

Liu

Zhang

et al. 2018

Environmental Toxicology

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“…Oxidative stress as a consequence of chemotherapy or radiotherapy or tissue inflammation promotes tissue damage, including damage to the vasculature by activating a series of signaling pathways (47,65). Moreover, accumulation of reactive oxygen species (ROS) causes cell apoptosis and necrosis and can further contribute to myofibroblast activation (10,72).…”

Section: Murine Wt Bm (Xrt/bm) Cells From C57bl/6 Donor Mice Into Thementioning

confidence: 99%

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

Klein

Steens

Wiesemann

et al. 2017

Antioxidants & Redox Signaling

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Aims: Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect to the vascular compartment remain elusive, and no causative radioprotective treatment is available to date. Results: The importance of injury to EC for radiation-induced late toxicity in lungs after whole thorax irradiation (WTI) was investigated using a mouse model of radiation-induced pneumopathy. We show that WTI induces EC loss as long-term complication, which is accompanied by the development of fibrosis. Adoptive transfer of mesenchymal stem cells (MSCs) either derived from bone marrow or aorta (vascular wall-resident MSCs) in the early phase after irradiation limited the radiation-induced EC loss and fibrosis progression. Furthermore, MSC-derived culture supernatants rescued the radiation-induced reduction in viability and longterm survival of cultured lung EC. We further identified the antioxidant enzyme superoxide dismutase 1 (SOD1) as a MSC-secreted factor. Importantly, MSC treatment restored the radiation-induced reduction of SOD1 levels after WTI. A similar protective effect was achieved by using the SOD-mimetic EUK134, suggesting that MSCderived SOD1 is involved in the protective action of MSC, presumably through paracrine signaling. Innovation: In this study, we explored the therapeutic potential of MSC therapy to prevent radiation-induced EC loss (late effect) and identified the protective mechanisms of MSC action. Conclusions: Adoptive transfer of MSCs early after irradiation counteracts radiation-induced vascular damage and EC loss as late adverse effects. The high activity of vascular wall-derived MSCs for radioprotection may be due to their tissue-specific action. Antioxid. Redox Signal. 26, 563-582.

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“…Lately, other authors established an irradiation (IR)-induced PF in C57BL/6 mice with 15 Gy on whole chest and then the mice were treated without or with TPL (i.v. 0.25 mg/kg, qod for 1 month) (Chen et al, 2016a). It demonstrated that TPL effectively reduced the IRinduced PF as evidenced by the less MFb, collagen deposition, ROS, and infiltrated AMs in the IR-lung tissue, as well as declined levels of NADPH oxidase (NOX)-2 and NOX-4 in AMs (Chen et al, 2016a).…”

Section: Terpenoidsmentioning

confidence: 93%

“…0.25 mg/kg, qod for 1 month) (Chen et al, 2016a). It demonstrated that TPL effectively reduced the IRinduced PF as evidenced by the less MFb, collagen deposition, ROS, and infiltrated AMs in the IR-lung tissue, as well as declined levels of NADPH oxidase (NOX)-2 and NOX-4 in AMs (Chen et al, 2016a). Its potential role in PF patients is encouraged to be included in the ongoing studies.…”

Section: Terpenoidsmentioning

confidence: 97%

Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

Kan

2017

Journal of Ethnopharmacology

107

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These research work have shown the therapeutic benefits of TCM in the treatment of PF. However, more continued researches should be undertaken to clarify the unconfirmed chemical composition and regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. The insights provided in present review will be needed for further exploration of botanical drugs in the development of PF therapy.

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Triptolide mitigates radiation-induced pulmonary fibrosis via inhibition of axis of alveolar macrophages-NOXes-ROS-myofibroblasts

Abstract: Our work demonstrated that the anti-fibrotic effect of TPL on IR-induced pulmonary fibrosis was related to its inhibition on the axis of alveolar macrophages-NOXes-ROS-myofibroblasts.

Cited by 32 publications

References 37 publications

Mechanisms involved in inflammatory pulmonary fibrosis induced by lunar dust simulant in rats

Mechanisms involved in inflammatory pulmonary fibrosis induced by lunar dust simulant in rats

Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression

Traditional Chinese medicine for pulmonary fibrosis therapy: Progress and future prospects

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