Triptolide alleviates radiation-induced pulmonary fibrosis via inhibiting IKKβ stimulated LOX production

Guo, Kaining; Chen, Jinran; Chen, Zhangjie; Luo, Gelian; Yang, Shanmin; Zhang, Mei; Hong, Jinsheng; Zhang, Lurong; Chen, Chun

doi:10.1016/j.bbrc.2020.04.023

Cited by 13 publications

(6 citation statements)

References 31 publications

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“…The LOX protein family, a cross-linked enzyme of the ECM, plays a key role in ECM remodeling and modification, regulating the development of fibrosis (Aumiller et al, 2017;Bellaye et al, 2018;Guo et al, 2020). Our study showed that the expressions of LOX and LOXL-2 were significantly increased in BLM-induced PF in mice (Figure 3).…”

Section: Discussionmentioning

confidence: 64%

“…In animal study, LOX inhibitors (β-Aminopropiononitrile) could reduce myocardial fibrosis and alleviating myocardial hypertrophy (Martínez-Martínez et al, 2016). Guo et al (2020) found that triptolide prevents nuclear translocation of NF-κB and DNA binding, effectively reducing the expression of LOX and alleviating the degree of radiation-induced PF in mice. Ikenaga et al found that selective targeting of LOXL2 inhibits the progression of liver fibrosis and accelerates its reversion (Ikenaga et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

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Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

et al. 2021

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Pulmonary fibrosis (PF) is a chronic and progressive process of tissue repair. Azithromycin (AZM) may be beneficial for the treatment of PF because AZM has anti-inflammatory and immune regulatory roles and inhibits remodeling, but the mechanism is not entirely clear. In this study, we established a mouse PF model induced by bleomycin (BLM) and primary mouse lung fibroblasts stimulated by transforming growth factor (TGF)-β1 to explore the possible mechanisms of AZM in PF. Results showed that AZM reduces mortality and lung inflammation and attenuates BLM-induced PF in mice. AZM effectively reduced the expression of α-smooth muscle actin (SMA) and type I collagen. Meanwhile, expression of lysyl oxidase (LOX) and lysyl oxidase-like protein (LOXL)-2 in the lung tissue of mice after AZM treatment was significantly lower than in the BLM group. In addition, this study found that AZM significantly inhibits the TGF-β1/Smad and JNK/c-Jun signaling pathways in vivo, and expression of a-SMA, type I collagen, LOX and LOXL-2 in the lung tissue of mice treated with AZM was significantly lower than that in the BLM group. In vitro, AZM also effectively inhibited type I collagen, LOX, LOXL-2 and JNK-c-Jun signaling pathways in TGF-β1-stimulated primary mouse fibroblasts, and this effect was similar to that of a JNK-specific inhibitor (SP600125). In conclusion, AZM effectively attenuated BLM-induced PF in mice, which may play a role by partially inhibiting the JNK/c-Jun and TGF-β1/Smad signaling pathways and reducing production of LOX and LOXL2.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

et al. 2021

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“…Promising radioprotective effects of triptolide have emerged from preclinical studies. Triptolide inhibited of IKKβ/NF-κB-mediated lysyl oxidase (LOX) production to reduce profibrotic IL-1β, IL-13 and TGF-β to diminish radiation-induced pulmonary fibrosis, and to improve mouse survival following radiation ( 168 , 169 ). Triptolide additionally reduced pulmonary fibrosis by reducing alveolar macrophage infiltration, phagocytosis and proinflammatory cytokine and chemokine production ( 170 ).…”

Section: Triptolide and Triptolide Analoguesmentioning

confidence: 99%

Natural biomolecules and derivatives as anticancer immunomodulatory agents

Bernitsa

Dayan²,

Stephanou³

et al. 2023

Front. Immunol.

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Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remodeling of the tumor immunosuppressive microenvironment and the sensitization of the immune system. This allows for improved recognition and targeting of cancer cells by the immune system and synergy with chemotherapeutics. In this review, we will discuss several well-known plant-derived biomolecules and examine their potential as immunomodulators, and therefore, as novel immunotherapies for cancer treatment.

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“…TPL could inhibit the infiltration, Inflammatory factors secretion, and phagocytosis of alveolar macrophages and eventually decrease paracrine activation of myofibroblasts [ 323 ]. TPL also inhibited the IKKβ/NF-κB pathway and thus reduces LOX production in fibroblasts [ 324 ].…”

Section: Advances In the Treatment Of Radiation-induced Fibrosismentioning

confidence: 99%

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

Yu,

Xu,

Song

et al. 2023

J Transl Med

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Cancer remains the leading cause of death around the world. In cancer treatment, over 50% of cancer patients receive radiotherapy alone or in multimodal combinations with other therapies. One of the adverse consequences after radiation exposure is the occurrence of radiation-induced tissue fibrosis (RIF), which is characterized by the abnormal activation of myofibroblasts and the excessive accumulation of extracellular matrix. This phenotype can manifest in multiple organs, such as lung, skin, liver and kidney. In-depth studies on the mechanisms of radiation-induced fibrosis have shown that a variety of extracellular signals such as immune cells and abnormal release of cytokines, and intracellular signals such as cGAS/STING, oxidative stress response, metabolic reprogramming and proteasome pathway activation are involved in the activation of myofibroblasts. Tissue fibrosis is extremely harmful to patients' health and requires early diagnosis. In addition to traditional serum markers, histologic and imaging tests, the diagnostic potential of nuclear medicine techniques is emerging. Anti-inflammatory and antioxidant therapies are the traditional treatments for radiation-induced fibrosis. Recently, some promising therapeutic strategies have emerged, such as stem cell therapy and targeted therapies. However, incomplete knowledge of the mechanisms hinders the treatment of this disease. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of radiation-induced fibrosis.

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Triptolide alleviates radiation-induced pulmonary fibrosis via inhibiting IKKβ stimulated LOX production

Cited by 13 publications

References 31 publications

Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

Natural biomolecules and derivatives as anticancer immunomodulatory agents

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

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