Thalidomide Alleviates Pulmonary Fibrosis Induced by Silica in Mice by Inhibiting ER Stress and the TLR4-NF-κB Pathway

Li, Yaqian; Cai, Wenchen; Jin, Fuyu; Wang, Xiaojing; Liu, Wenjing; Li, Tian; Yang, Xinyu; Liu, Heliang; Xu, Hong; Fang, Yang

doi:10.3390/ijms23105656

Cited by 7 publications

(2 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF-α, as a downstream factor of the TLR4-NF-κB signaling pathway, is significantly down-regulated. 37 This is consistent with our experimental results, in our rosacea mice model, thalidomide could reduce the skin lesion area and inhibit inflammation by reducing the infiltration of inflammatory cells and the expression of TNF-α and IL-1β. Intestinal fibrosis is considered to be a common phenomenon in inflammatory bowel diseases.…”

Section: Discussionsupporting

confidence: 92%

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Kang¹,

Zhang²,

He³

et al. 2022

DDDT

Self Cite

View full text Add to dashboard Cite

Purpose Most of the existing studies focus on the early inflammation of rosacea, with few interventions on the later development of fibrosis and the relationship between thalidomide and rosacea. The purpose of this study was to construct a long-term induction model and explore the effects of thalidomide on the later stage of inflammation and early stage of fibrosis in rosacea. Patients and Methods BALB/c male mice were randomly divided into four groups: control group, control plus thalidomide group, LL-37 group and LL-37 plus thalidomide group, Intradermal and intraperitoneal injections were given. After repeated induction, skin changes were recorded by taking photos. The animals were sacrificed, the back skin was used for HE staining and VG staining to detect histomorphological characteristics. Immunofluorescence staining and Western blot were used to detect the expression of inflammatory and fibrosis-related factors. Results The results were compared with the early stage of the model, wherein the skin inflammation of the 20-day mice was more obvious with a trend of fibrosis. Compared with the control group, histopathological examination showed that the inflammatory cell infiltration in the LL-37 group was significantly increased, and the skin was thickened with collagen deposition. LL-37 induction significantly increased the expression of inflammatory markers (eg, TNF-α and IL-1β) and fibrotic markers (eg, COL1, α-SMA, vimentin and N-Cadherin). Intervention with thalidomide significantly reduced erythema, inflammatory cell infiltration, collagen deposition, and down-regulate the expression of inflammation and fibrosis related factors in rosacea mice. Conclusion The long-term continuous induction of LL-37 in mice could simulate the occurrence and development of rosacea, and thalidomide could ameliorate the rosacea induced by long-term exposure to LL-37 by regulating inflammatory infiltration, collagen deposition and fibrosis-related processes.

show abstract

Section: Discussionsupporting

confidence: 92%

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Kang¹,

Zhang²,

He³

et al. 2022

DDDT

Self Cite

View full text Add to dashboard Cite

show abstract

“…This suggests that thalidomide inhibits angiogenesis via downregulation of VEGF and angiopoietin-2 in Crohn's Disease (Wang et al 2021 ) 37 Thalidomide protected against paraquat-induced lung injury through a miRNA-141/HDAC6/IκBα-NF-κB axis in rat lung fibrosis model and in the RLE-6TN cell model (Zheng et al 2021 ) 38 Thalidomide modulated ER-stress, through TLR4- NF-κB pathway in mouse model of silicosis. Silicosis is a common form of pulmonary fibrosis in China (Li et al 2022b ) 39 Thalidomide derivative CC-885 was found to be a Basonuclin 2 (BNC2) inhibitor. The transcript BCN2 is responsible for simulating fibrosis signalling in tissues (Bobowski-Gerard et al 2022 ) 40 Thalidomide effectively lowered skin lesions, inflammation and fibrosis related factors in rosacea mice model (Kang et al 2022 ) …”

Section: Introductionmentioning

confidence: 99%

Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis

et al. 2023

View full text Add to dashboard Cite

The “Thalidomide tragedy” is a landmark in the history of the pharmaceutical industry. Despite limited clinical trials, there is a continuous effort to investigate thalidomide as a drug for cancer and inflammatory diseases such as rheumatoid arthritis, lepromatous leprosy, and COVID-19. This review focuses on the possibilities of targeting inflammation by repurposing thalidomide for the treatment of idiopathic pulmonary fibrosis (IPF). Articles were searched from the Scopus database, sorted, and selected articles were reviewed. The content includes the proven mechanisms of action of thalidomide relevant to IPF. Inflammation, oxidative stress, and epigenetic mechanisms are major pathogenic factors in IPF. Transforming growth factor-β (TGF-β) is the major biomarker of IPF. Thalidomide is an effective anti-inflammatory drug in inhibiting TGF-β, interleukins (IL-6 and IL-1β), and tumour necrosis factor-α (TNF-α). Thalidomide binds cereblon, a process that is involved in the proposed mechanism in specific cancers such as breast cancer, colon cancer, multiple myeloma, and lung cancer. Cereblon is involved in activating AMP-activated protein kinase (AMPK)-TGF-β/Smad signalling, thereby attenuating fibrosis. The past few years have witnessed an improvement in the identification of biomarkers and diagnostic technologies in respiratory diseases, partly because of the COVID-19 pandemic. Hence, investment in clinical trials with a systematic plan can help repurpose thalidomide for pulmonary fibrosis. Graphical Abstract

show abstract

ISRIB inhibits the senescence of type II pulmonary epithelial cells to alleviate pulmonary fibrosis induced by silica in mice

Li,

An,

Jin

et al. 2023

Ecotoxicology and Environmental Safety

View full text Add to dashboard Cite

Thalidomide Alleviates Pulmonary Fibrosis Induced by Silica in Mice by Inhibiting ER Stress and the TLR4-NF-κB Pathway

Cited by 7 publications

References 49 publications

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Thalidomide Attenuates Skin Lesions and Inflammation in Rosacea-Like Mice Induced by Long-Term Exposure of LL-37

Thalidomide interaction with inflammation in idiopathic pulmonary fibrosis

ISRIB inhibits the senescence of type II pulmonary epithelial cells to alleviate pulmonary fibrosis induced by silica in mice

Contact Info

Product

Resources

About