Tumor Necrosis Factor Receptor 2 (TNFR2)·Interleukin-17 Receptor D (IL-17RD) Heteromerization Reveals a Novel Mechanism for NF-κB Activation

Yang, Sherry; Wang, Yinyin; Mei, Kunrong; Zhang, Sen; Sun, X. F.; Ren, Fei; Liu, Sihan; Yang, Zheng; Wang, Xinquan; Qin, Zhihai; Chen, Zhijie

doi:10.1074/jbc.m114.586560

Cited by 28 publications

(39 citation statements)

References 30 publications

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“…The complex between IL-17RD and TNFR2 was shown to be formed in HK-2 and 786-O cell lines (a human proximal tubular cell line derived from normal kidney and a human renal cell adenocarcinoma cell line, respectively), and also in rat and mouse renal tissue. This indicates that the interaction between TNFR2 and IL-17RD may arise under physiological conditions [237].…”

Section: Interaction Between Tnfr2 and Interleukin-17 Receptor Dmentioning

confidence: 93%

“…For example, it was very recently demonstrated that TNFR2 (but not TNFR1) can form a heteromer with interleukin-17 receptor D (IL-17RD, also known as Sef), leading to activation of NF-κB signaling via TRAF2 recruitment [237]. Depletion of IL-17RD was found to impair TNFR2-mediated activation of NF-κB.…”

Section: Interaction Between Tnfr2 and Interleukin-17 Receptor Dmentioning

confidence: 99%

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Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

et al. 2015

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Numerous studies have revealed the pleiotropic functions of tumor necrosis factor alpha (TNF-α), and have linked it with several neurodegenerative disorders. This review describes the signaling pathways induced by TNF-α via its two receptors (TNFR1 and TNFR2), and their functions in neurodegenerative processes as in Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and ischemic stroke. It has become clear that TNF-α may exert divergent actions in neurodegenerative disorders, including neurodegenerative and neuroprotective effects, which appear to depend on its signaling via either TNFR1 or TNFR2. Specific targeting of these receptors is a promising therapeutic strategy for many disorders.

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Section: Interaction Between Tnfr2 and Interleukin-17 Receptor Dmentioning

confidence: 93%

Section: Interaction Between Tnfr2 and Interleukin-17 Receptor Dmentioning

confidence: 99%

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

et al. 2015

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“…The gene product affects fibroblast growth factor signaling, inhibiting or stimulating growth through MAPK/ERK signaling 49 . It also interacts with TNF receptor 2 (TNFR2) to activate NF-κB 59 . Integrin subunit beta 8 ( ITGB8 ) at 7p21.1 is a member of the integrin beta chain family and ITGB8 protein expression protein is increased in COPD 60–62 .…”

Section: Discussionmentioning

confidence: 99%

Expanded genetic landscape of chronic obstructive pulmonary disease reveals heterogeneous cell type and phenotype associations

Sakornsakolpat

Prokopenko

Lamontagne

et al. 2018

Preprint

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SummaryChronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide novel insights into disease pathogenesis. To broaden COPD genetic risk loci discovery and identify cell type and phenotype associations we performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci with P value < 5×10−8; 47 were previously described in association with either COPD or population-based lung function. Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and alveolar type II cells. We found 9 shared genomic regions between COPD and asthma and 5 between COPD and pulmonary fibrosis. COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations. Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD.

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“…According to D’Hulst et al, observations of reduced T-lymphocyte activation in the lungs of mice lacking TNFR2 and high lymphocyte numbers in bronchoalveolar lavage fluid of TNFR1 knockout (KO) mice exclusively expressing TNFR2 then further underline the importance of the R2 receptor in T-cell proliferation 22. NFκB activation can also be induced by TNFR2 that can be activated by TNFα to further activate NFκB 15. Therefore, the present data confirm the importance of this marker in COPD pathogenesis and that, although both TNFRs are involved in long-term cigarette smoke-induced pulmonary inflammation and emphysema, the contribution of TNFR2 is most prominent.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, soluble forms of the receptor (sRAGE), shed from the plasma membrane via proteolytic cleavage by matrix metalloproteinases, have been shown to be protective in preventing signaling through mRAGE 14. Another mechanism of NFκB activation is through tumor necrosis factor alpha (TNF-α) receptors (TNFR); both TNFR1 and TNFR2 activation can lead to stimulation of nuclear factor NFκB in a variety of cells 15,16. Therefore, AGE, RAGE, and TNFR stimulate NFκB and can trigger the production of proinflammatory cytokines leading to inflammation in smokers and patients with COPD 11–15,17…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor receptor 2 as a possible marker of COPD in smokers and ex-smokers

Caram¹,

Ferrari²,

Nogueira³

et al. 2017

COPD

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IntroductionOxidative stress and systemic inflammation are higher in smokers and patients with COPD; however, markers that may help differentiate between smokers and patients with COPD have not yet been identified. We hypothesized that tumor necrosis factor-alpha receptor (TNFR) and soluble form of the receptor for advanced glycation end products (sRAGE) can be indicators of COPD in asymptomatic patients.Patients and methodsWe evaluated 32 smokers (smoking history >10 pack-years), 32 patients with mild/moderate COPD (smokers and ex-smokers), and 32 never smokers. Concentrations of C-reactive protein (CRP), interleukin (IL)-6, TNFR1 and TNFR2, advanced glycation end products (AGEs), and the sRAGE were measured in serum.ResultsThere were higher CRP and AGEs concentrations in smokers and in patients with COPD (P<0.001 and P=0.01, respectively) compared to controls, without statistical difference between smokers and patients with COPD. Concentrations of sRAGE, IL-6, and TNFR1 did not differ between study groups. TNFR2 was significantly higher in patients with COPD than in smokers (P=0.004) and controls (P=0.004), and the presence of COPD (P=0.02) and CRP (P=0.001) showed a positive association with TNFR2. Positive associations for smoking (P=0.04), CRP (P=0.03), and IL-6 (P=0.03) with AGEs were also found. The interaction variable (smoking × COPD) showed a positive association with IL-6.ConclusionOur data suggest that TNFR2 may be a possible marker of COPD in asymptomatic smokers and ex-smokers. Although smokers and patients with early COPD presented other increased systemic inflammation markers (eg, CRP) and oxidative stress (measured by AGEs), they did not differentiate smokers from COPD.

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Tumor Necrosis Factor Receptor 2 (TNFR2)·Interleukin-17 Receptor D (IL-17RD) Heteromerization Reveals a Novel Mechanism for NF-κB Activation

Cited by 28 publications

References 30 publications

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

Expanded genetic landscape of chronic obstructive pulmonary disease reveals heterogeneous cell type and phenotype associations

Tumor necrosis factor receptor 2 as a possible marker of COPD in smokers and ex-smokers

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