Combined signaling of NF-kappaB and IL-17 contributes to Mesenchymal stem cells-mediated protection for Paraquat-induced acute lung injury

Zhang, Lichun; Wang, Yu; Shen, Haitao; Zhao, Min

doi:10.1186/s12890-020-01232-5

Cited by 13 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once NF-κB is activated, it translocates to the nucleus and binds with promoter regions, inducing target transcription of inflammatory factors, cytokines, and chemokines ( Wu et al, 2022 ). According to our results, p-IKKα/β, p-IκBα, and p-p65 levels were significantly attenuated in the hAMSC-transplanted groups, which was consistent with previous reports ( Yang et al, 2011 ; Wang et al, 2016 ; Zhang et al, 2018 ; Zhang et al, 2020 ). Therefore, hAMSCs might inhibit the NK-κB pathway by blocking the inflammatory cascade and the progression of ALI ( Figure 9 ).…”

Section: Discussionsupporting

confidence: 93%

“…Then, the mechanism of MSC therapy was discussed, which might involve multiple signaling pathways. Considering that LPS and PQ stimulate the production of proinflammatory factors and reactive oxygen nitrogen species (RONS), they may exacerbate inflammation and tissue damage via the NF-κB signaling pathway ( Zhang et al, 2019a ; Xiao et al, 2020 ; Zhang et al, 2020 ). In normal cells, p50 is inactive as a heterodimer with p65 (orc-Rel) through its interaction with inhibitory IκB proteins.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Human amnion-derived mesenchymal stem cells attenuate acute lung injury in two different acute lung injury mice models

Sun

Qin

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Acute lung injury (ALI) is one of the most common clinical emergencies with limited effective pharmaceutical treatment in the clinic, especially when it progresses to acute respiratory distress syndrome (ARDS). Currently, mesenchymal stem cells (MSCs) exhibit specific superiority for ALI/ARDS treatment. However, stem cells from different sources may result in controversial effects on similar disease conditions. This study aimed to determine the effects of human amnion-derived mesenchymal stem cells (hAMSCs) on two different ALI mice model. The administered hAMSCs effectively accumulated in the lung tissues in all hAMSC-treated groups. Compared with the model and 1% human serum albumin (HSA) groups, high-dose hAMSCs (1.0 × 106 cells) group significantly alleviated alveolar-capillary permeability, oxidative stress, inflammatory factors level and histopathological damage. In addition, the NF-κB signaling pathway is one of the key pathways activated during lipopolysaccharide (LPS) or paraquat (PQ)-induced lung injury. Our results indicated that hAMSCs (1.0 × 106 cells) obviously inhibited the expression of p-IKKα/β, p-IκBα, and p-p65 in the lung tissue (p < 0.05). The high-dose (HD) hAMSC treatment exerted beneficial therapeutic effects on ALI mice models without detectable adverse reactions. The therapeutic effect of hAMSCs might involve NF-κB signaling pathway inhibition. hAMSC treatment is a potential candidate therapy for ALI.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Human amnion-derived mesenchymal stem cells attenuate acute lung injury in two different acute lung injury mice models

Sun

Qin

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…16,17 Similarly, the IL-17 signaling pathway is determinant for the pathogenesis of PQ-induced toxicity. 18 Reduced IL-17 signaling protects against PQ-induced lung injury. 19 In the PPI network, 10 hub genes were identified: Atf3 , Ddit3 , Trib3 , Ptgs2 , Chac1 , Areg , Gadd45a , Csf2 , Ereg , and Cxcl2 .…”

Section: Discussionmentioning

confidence: 99%

Treatment with paraquat affects the expression of ferroptosis-related genes

Cai

Zhang

et al. 2023

Hum Exp Toxicol

View full text Add to dashboard Cite

Objective We aimed to explore the mechanisms underlying paraquat (PQ)-induced damage using cell lines (NCTC1469, TC-1, TCMK-1) and bioinformatic analysis of the GSE153959 dataset. Assessment of changes in the expression of ferroptosis-related genes in cellular damage due to paraquat poisoning and the important value of these genes in the pathogenesis. Methods Data were retrieved from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) related to ferroptosis were identified by Venn plots and analyzed for enrichment. Proteins encoded by these DEGs were studied for interactions. qRT-PCR and western blotting analyses of cultured cells were used to determine the expression of ferroptosis-related DEGs and their corresponding protein levels. Results We identified 25 DEGs primarily involved in epidermal growth factor receptor signaling, apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and ferroptosis. From these, we uncovered eight ferroptosis-related DEGs, four of which were involved in ER response and regulators of ferroptosis— Chac1 (ChaC glutathione specific gamma-glutamylcyclotransferase 1), Atf3 (activating transcription factor 3), Tfrc (transferrin receptor), and Slc7a11 (solute carrier family 7 member 11). Significant changes in mRNA and protein levels of CHAC1, ATF3, TFRC, and SLC7A11 were confirmed in PQ-exposed cells. Conclusion ER stress and ferroptosis are critical for PQ-induced cell damage. CHAC1, ATF3, TFRC, and SLC7A11 are essential molecules implicated in PQ-induced ferroptosis that may serve as therapeutic targets for the amelioration of PQ poisoning.

show abstract

“…T regulatory type 1 (TR1) cells secrete high levels of the anti-inflammatory IL-10 [ 31 ], whereas TH17 cells are characterized by secretion of IL-17 [ 32 ]. TGF- β 1 supports the conversion of TH17 to TR1 [ 33 , 34 ]. Taken together, these results indicate that TH17 cells might transdifferentiate into TR1 cells induced by a high concentration of TGF- β 1 in the model group, and the decrease in the concentration of TGF- β 1 leads to a decrease in the conversion of TH17 to TR1, resulting in an increase in the concentration of TH17 and a decrease in its concentration.…”

Section: Discussionmentioning

confidence: 99%

Human Amnion-Derived MSCs Alleviate Acute Lung Injury and Hinder Pulmonary Fibrosis Caused by Paraquat in Rats

Wang

Liao

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background/Aims. Paraquat is an effective herbicide used worldwide. Due to high lung toxicity and a lack of effective treatment, elevated morbidity and mortality occur after ingestion. Mesenchymal stem cells (MSCs) may be an option for repairing, remodeling, or regenerating lungs damaged by paraquat. Human amnion-derived mesenchymal stem cells (hAD-MSCs) have significant biological advantages including low immunogenicity and noninvasive acquisition for acute and chronic lung injury. In this study, the preclinical efficacy of hAD-MSCs in treating paraquat-induced acute lung injury and pulmonary fibrosis was investigated. Clinical cell therapy was replicated including the dose and timing of hAD-MSC treatment. Methods. First, the purity of hAD-MSCs was determined by morphological observation and FCM, and the effects on the survival of paraquat-poisoned Sprague-Dawley rats were observed. All rats were randomly divided into three groups, defined as the sham control group ( n = 8 ), model group ( n = 15 ), and hAD-MSC-transplanted group ( n = 17 ). Pneumonocyte damage and inflammatory cell infiltration were investigated in the three groups of rats, untreated control, paraquat only, and paraquat+hAD-MSC transplanted, using H&E staining. Fibrosis was investigated in three groups of rats using Masson’s trichrome staining and Sirius red staining. The profibrotic factor TGF-β1, the composition of fibrotic collagen HYP, and the hAD-MSC-secreted immunosuppressive factor HLA-G5 in serum were investigated in the three groups of rats using ELISA. Furthermore, the distribution of hAD-MSCs was investigated in the three groups of rats using immunohistochemistry and hematoxylin staining. Results. The hAD-MSCs exhibited typical hallmarks of MSCs, improved the state of being and survival of paraquat-poisoned rats, reduced both lung injury and inflammation, and inhibited the progression of pulmonary fibrosis by decreasing the deposition of collagen and the secretion of both TGF-β1 and HYP. The hAD-MSCs could survive in damaged lungs and secreted appropriate amounts of HLA-G5 into the serum. Conclusion. The obtained results indicate that hAD-MSCs used to treat paraquat-induced lung injury may work through anti-inflammatory and immunosuppressive pathways and the downregulation of profibrotic elements. This study suggests that the transplantation of hAD-MSCs is a promising therapeutic approach for the treatment of paraquat-intoxicated patients.

show abstract

Combined signaling of NF-kappaB and IL-17 contributes to Mesenchymal stem cells-mediated protection for Paraquat-induced acute lung injury

Cited by 13 publications

References 32 publications

Human amnion-derived mesenchymal stem cells attenuate acute lung injury in two different acute lung injury mice models

Human amnion-derived mesenchymal stem cells attenuate acute lung injury in two different acute lung injury mice models

Treatment with paraquat affects the expression of ferroptosis-related genes

Human Amnion-Derived MSCs Alleviate Acute Lung Injury and Hinder Pulmonary Fibrosis Caused by Paraquat in Rats

Contact Info

Product

Resources

About