TNF-Î± induces TGF-Î²<sub>1</sub>expression in lung fibroblasts at the transcriptional level<i>via</i>AP-1 activation

Sullivan, Deborah E.; Ferris, MaryBeth; Nguyen, Hong T.; Abboud, Elizabeth; Brody, Arnold R.

doi:10.1111/j.1582-4934.2009.00647.x

Cited by 71 publications

(50 citation statements)

References 46 publications

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“…These data suggested that the antifibrotic action of rotenone is possibly through its blockade of TGF- β 1 , at least to some extent. Reduction of TGF- β 1 could be secondary to the attenuation of oxidative stress and inflammation because both ROS [38] and inflammatory cytokines [39] have been shown to be responsible for the TGF- β 1 induction.…”

Section: Discussionmentioning

confidence: 99%

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Sun

Zhang

Zhao

et al. 2014

Mediators of Inflammation

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Mitochondrial abnormality has been shown in many kidney disease models. However, its role in the pathogenesis of chronic kidney diseases (CKDs) is still uncertain. In present study, a mitochondrial complex I inhibitor rotenone was applied to the mice subjected to unilateral ureteral obstruction (UUO). Following 7-days rotenone treatment, a remarkable attenuation of tubular injury was detected by PAS staining. In line with the improvement of kidney morphology, rotenone remarkably blunted fibrotic response as shown by downregulation of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), collagen I, collagen III, and α-SMA, paralleled with a substantial decrease of TGF-β 1. Meanwhile, the oxidative stress markers thiobarbituric acid-reactive substances (TBARS) and heme oxygenase 1 (HO-1) and inflammatory markers TNF-α, IL-1β, and ICAM-1 were markedly decreased. More importantly, the reduction of mitochondrial DNA copy number and mitochondrial NADH dehydrogenase subunit 1 (mtND1) expression in obstructed kidneys was moderately but significantly restored by rotenone, suggesting an amelioration of mitochondrial injury. Collectively, mitochondrial complex I inhibitor rotenone protected kidneys against obstructive injury possibly via inhibition of mitochondrial oxidative stress, inflammation, and fibrosis, suggesting an important role of mitochondrial dysfunction in the pathogenesis of obstructive kidney disease.

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Section: Discussionmentioning

confidence: 99%

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Sun

Zhang

Zhao

et al. 2014

Mediators of Inflammation

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“…In contrast, TNFα promotes production of ECM by murine intestinal myofibroblasts in vitro . Notably, others have shown that TNFα stimulation of the murine 3T3 fibroblast cell line stimulated the expression of TGFβ [40]. Thus, while stimulation of esophageal epithelial cells with TGFβ induced higher levels of mesenchymal genes compared to TNFα, it is possible that TNFα may similarly exert a more potent effect upon myofibroblast-like function via upregulation of additional profibrotic genes, including TGFβ.…”

Section: Discussionmentioning

confidence: 99%

Esophageal epithelial cells acquire functional characteristics of activated myofibroblasts after undergoing an epithelial to mesenchymal transition

Muir

Dods

Noah

et al. 2015

Experimental Cell Research

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Background and Aims Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that leads to esophageal fibrosis and stricture. We have recently shown that in EoE, esophageal epithelial cells undergo an epithelial to mesenchymal transition (EMT), characterized by gain of mesenchymal markers and loss of epithelial gene expression. Whether epithelial cells exposed to profibrotic cytokines can also acquire the functional characteristics of activated myofibroblasts, including migration, contraction, and extracellular matrix deposition, is relevant to our understanding and treatment of EoE-associated fibrogenesis. In the current study, we characterize cell migration, contraction, and collagen production by esophageal epithelial cells that have undergone cytokine-induced EMT in vitro. Methods and Results Stimulation of human non-transformed immortalized esophageal epithelial cells (EPC2-hTERT) with profibrotic cytokines TNFα, TGFβ, and IL1β for three weeks led to acquisition of mesenchymal αSMA and vimentin, and loss of epithelial E-cadherin expression. Upon removal of the profibrotic stimulus, epithelial characteristics were partially rescued. TGFβ stimulation had a robust effect upon epithelial collagen production. Surprisingly, TNFα stimulation had the most potent effect upon cell migration and contraction, exceeding the effects of the prototypical profibrotic cytokine TGFβ. IL1β stimulation alone had minimal effect upon esophageal epithelial migration, contraction, and collagen production. Conclusions Esophageal epithelial cells that have undergone EMT acquire functional characteristics of activated myofibroblasts in vitro. Profibrotic cytokines exert differential effects upon esophageal epithelial cells, underscoring complexities of fibrogenesis in EoE, and implicating esophageal epithelial cells as effector cells in EoE-associated fibrogenesis.

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“…Currently, there is increasing evidence that TNF-α is important in the initiation and perpetuation of the fibrotic process 49–54. In a recent study, Sullivan et al demonstrated that TNF-α induces TGF-β1 expression in lung fibroblasts 49.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, Sullivan et al demonstrated that TNF-α induces TGF-β1 expression in lung fibroblasts 49. Battegay et al reported that TNF-α stimulates DNA synthesis and proliferation of cultured human fibroblasts and that there is a strong relationship between secretion of PDGF and TNF-α stimulation 50.…”

Section: Discussionmentioning

confidence: 99%

Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery

Turgut¹,

Eren²,

Akın³

et al. 2014

DDDT

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BackgroundThe purpose of this work was to look into the effects of infliximab on wound healing in experimental glaucoma filtration surgery and to compare the antifibrotic effects of this agent to that of mitomycin-C (MMC).MethodsTwenty-eight male New Zealand White rabbits were randomly assigned to four groups, each including seven rabbits: control group, sham group, MMC group, and infliximab group. The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the MMC treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the infliximab treatment group underwent trabeculectomy and one drop of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery. On day 14 of the experiment, the operated and control eyes were enucleated and histologically and immunohistochemically analyzed.ResultsThe mean fibroblast and mononuclear cell (MNC) numbers and the mean immunostaining intensities of transforming growth factor-β (TGF-β), fibroblast growth factor-β (FGF-β), and platelet-derived growth factor (PDGF) in the sham group were higher than those of the control group (P<0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-β, FGF-β, and PDGF in the MMC and infliximab groups were statistically significantly lower than those of the sham group (P<0.01). The mean fibroblast and MNC numbers and the mean TGF-β, FGF-β, and PDGF immunostaining intensities of the MMC and infliximab groups were similar (P>0.05).ConclusionOur study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers and immunostaining intensities of TGF-β, FGF-β, and PDGF.

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TNF-Î± induces TGF-Î²₁expression in lung fibroblasts at the transcriptional levelviaAP-1 activation

Cited by 71 publications

References 46 publications

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Esophageal epithelial cells acquire functional characteristics of activated myofibroblasts after undergoing an epithelial to mesenchymal transition

Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery

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TNF-Î± induces TGF-Î²1expression in lung fibroblasts at the transcriptional levelviaAP-1 activation

Cited by 71 publications

References 46 publications

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Esophageal epithelial cells acquire functional characteristics of activated myofibroblasts after undergoing an epithelial to mesenchymal transition

Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery

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Resources

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TNF-Î± induces TGF-Î²₁expression in lung fibroblasts at the transcriptional levelviaAP-1 activation