Role of TLR4‐MAP4K4 signaling pathway in models of oxygen‐induced retinopathy

Chen, Wenwen; Zhang, Juan; Zhang, Peijun; Hu, Fangyuan; Gu, Jianying; Chang, Qing

doi:10.1096/fj.201801086rr

Cited by 12 publications

(12 citation statements)

References 48 publications

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“…TLR members play an important role in recognizing pathogen-associated molecular patterns and are crucial components in the innate immunity (31). Earlier studies have shown that the interaction between TLRs and myeloid differentiation protein 88 further activates MAPK p38, JNK, and NF-kB, which is essential to produce cytokines such as IL IL-6, IL-8, and TNF-a (32).…”

Section: Discussionmentioning

confidence: 99%

RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1–TLR4–NF‐κB pathway in macrophages

et al. 2019

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Liver fibrosis is an important pathologic process in injured liver tissues. A protein kinase, receptor‐interacting protein (RIP)3, plays a crucial role in mediating different diseases. However, the role of RIP3 in macrophages in liver fibrosis has not yet been studied. In our study, we found that RIP3 expression was up‐regulated in liver tissues and macrophages of humans and mice with liver fibrosis. Absence of RIP3 in macrophages could alleviate inflammation and macrophage or neutrophil accumulation in mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. Importantly, RIP3 deficiency in macrophages could decrease CCl4‐induced and BDL‐induced liver fibrosis in mice. Moreover, RIP3 deficiency could inhibit the TLR4–NF‐κB pathway through suppressing Rho‐associated coiled‐coil containing protein kinase (ROCK)l in macrophages. To explore the connection of ROCK1 and RIP3 in macrophages of mice with liver fibrosis in vivo, ROCK1‐overexpressed macrophages were infused to RIP3‐deficient mice, which resulted in increased inflammation and liver fibrosis. In conclusion, our findings suggest that RIP3 plays a crucial proinflammatory role in liver fibrosis by regulating the ROCK1–TLR4–NF‐κB signaling pathway in macrophages and therefore may be a potential therapeutic target for immune‐mediated liver fibrosis.—Wei, S., Zhou, H., Wang, Q., Zhou, S., Li, C, Liu, R., Qiu, J., Shi, C, Lu, L. RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1‐TLR4‐NF‐κB pathway in macrophages. FASEB J. 33, 11180–11193 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1–TLR4–NF‐κB pathway in macrophages

et al. 2019

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“…This is a reasonable result because the structure of ranibizumab is similar to that of bevacizumab Fab, which lacks the ability to interact with mouse VEGF. 29,30 Since there are many articles about the use of ranibizumab as an effective anti-VEGF drug in mice, [17][18][19][20][21][22][23] we believe it is necessary to alert ophthalmology researchers against using ranibizumab as an anti-VEGF drug in the future mouse experiments.…”

Section: Discussionmentioning

confidence: 99%

“…It is unclear why ranibizumab showed anti-VEGF effects in previous reports, [17][18][19][20][21][22] but we suspect that the use of poor quantitative methods such as uorescein angiography, 19 immunostaining of retinal sections, [18][19][20] or uorescein isothiocyanate (FITC)-dextran perfused retinal at mounts 18,20 may have led to different results. Fluorescein angiography is suitable for qualitative analysis, but not quantitative analysis because the amount of ash light and the timing of the photography after uorescein injection may cause the results to vary.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Currently, bevacizumab, ranibizumab, and a ibercept are the major anti-VEGF drugs in ophthalmic practice. 12 Accordingly, bevacizumab, [13][14][15][16] ranibizumab, [17][18][19][20][21][22][23] and a ibercept [24][25][26][27][28] are frequently used in experiments with mouse models of retinal vascular diseases. Notably, Ferrara N et al reported that bevacizumab's ability to neutralize VEGF was species speci c and lacking in mice.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Mouse VEGF Neutralization by Ranibizumab and Aflibercept

Ichiyama¹,

Matsumoto²,

Obata³

et al. 2021

Preprint

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There are many articles using bevacizumab, ranibizumab, and aflibercept as effective anti-vascular endothelial growth factor (VEGF) drugs in mice. However, it has been reported that bevacizumab lacks the ability to neutralize mouse VEGF. Here, we assessed the interaction between ranibizumab or aflibercept and mouse VEGF, both in vitro and in vivo. In vitro, we analyzed the interaction of mouse VEGF-A with aflibercept or ranibizumab as the primary antibody by Western blot, and observed immunoreactive bands for mouse VEGF-A in the aflibercept-probed blot, but not in the ranibizumab-probed blot. In vivo, we assessed the effect of intravitreal injection of ranibizumab and aflibercept on oxygen induced retinopathy and the effect of multiple intraperitoneal injections of ranibizumab and aflibercept on neonatal mice, and found that anti-VEGF effects were observed with aflibercept, but not with ranibizumab in both experiments. Our results suggest that aflibercept but not ranibizumab interacts with mouse VEGF. When conducting experiments using anti-VEGF drugs in mice, aflibercept is suitable, but ranibizumab is not.

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“…TLR4 levels are raised in response to retinal IR injury (13,140,142,(146)(147)(148)(149) and hypoxia (7,150). In particular, TLR4 levels are highly expressed in the INL (13,146) and GCL (13,142,146) following I/R injury.…”

Section: Inflammatory Pathwaysmentioning

confidence: 99%

Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases

2022

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There is growing evidence that the pathogenesis of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) have a significant chronic inflammatory component. A vital part of the inflammatory cascade is through the activation of pattern recognition receptors (PRR) such as toll-like receptors (TLR). Here, we reviewed the past and current literature to ascertain the cumulative knowledge regarding the effect of TLRs on the development and progression of retinal diseases. There is burgeoning research demonstrating the relationship between TLRs and risk of developing retinal diseases, utilising a range of relevant disease models and a few large clinical investigations. The literature confirms that TLRs are involved in the development and progression of retinal diseases such as DR, AMD, and ischaemic retinopathy. Genetic polymorphisms in TLRs appear to contribute to the risk of developing AMD and DR. However, there are some inconsistencies in the published reports which require further elucidation. The evidence regarding TLR associations in retinal dystrophies including retinitis pigmentosa is limited. Based on the current evidence relating to the role of TLRs, combining anti-VEGF therapies with TLR inhibition may provide a longer-lasting treatment in some retinal vascular diseases.

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Role of TLR4‐MAP4K4 signaling pathway in models of oxygen‐induced retinopathy

Cited by 12 publications

References 48 publications

RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1–TLR4–NF‐κB pathway in macrophages

RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1–TLR4–NF‐κB pathway in macrophages

Assessment of Mouse VEGF Neutralization by Ranibizumab and Aflibercept

Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases

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