tnf receptor
Recently Published Documents


TOTAL DOCUMENTS

1462
(FIVE YEARS 169)

H-INDEX

116
(FIVE YEARS 7)

2022 ◽  
pp. ji2001358
Author(s):  
Eigo Kawahara ◽  
Mitsuki Azuma ◽  
Hiroyuki Nagashima ◽  
Koki Omori ◽  
Sho Akiyama ◽  
...  

2022 ◽  
Author(s):  
Yao Chen ◽  
Lei Tong ◽  
Peng-Yin Nie ◽  
Yu-Lu Chen ◽  
Lili Ji

Abstract BackgroundMicroRNA-124-3p (miR-124) plays an important role in neuroprotective functions in various neurological disorders, but whether miR-124 participates in the pathological progression of posttraumatic stress disorder (PTSD) remains poorly understood. MethodsIn the present study, we evaluated the level of neuroinflammation in the hippocampus of rats exposed to single-prolonged stress (SPS) by western blot and immunofluorescence staining, while the effect of miR-124 on PTSD-like behaviors was evaluated by behavioral test. ResultsOur results demonstrated that the level of miR-124 in the hippocampus of rats exposed to SPS was downregulated and that the upregulation of miR-124 could alleviate the PTSD-like behaviors of SPS rats. This effect of miR-124 might be achieved through TNF receptor-associated Factor 6 (TRAF6), which is a target gene of miR-124 and plays an important role in the immune and inflammatory reaction by regulating nuclear factor kappa-B (NF-κB). Furthermore, we found that miR-124 not only decreased the level of proinflammatory cytokines but also increased the expression levels of synaptic proteins (PSD95 and synapsin I) and regulated the morphology of neurons. ConclusionThese results suggested that miR-124 might attenuate PTSD-like behaviors and decrease the level of proinflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats exposed to SPS.


Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 132
Author(s):  
Zhenqiang Yao ◽  
Stephen J. Getting ◽  
Ian C. Locke

Increased osteoclast (OC) differentiation and activity is the critical event that results in bone loss and joint destruction in common pathological bone conditions, such as osteoporosis and rheumatoid arthritis (RA). RANKL and its decoy receptor, osteoprotegerin (OPG), control OC differentiation and activity. However, there is a specific concern of a rebound effect of denosumab discontinuation in treating osteoporosis. TNFα can induce OC differentiation that is independent of the RANKL/RANK system. In this review, we discuss the factors that negatively and positively regulate TNFα induction of OC formation, and the mechanisms involved to inform the design of new anti-resorptive agents for the treatment of bone conditions with enhanced OC formation. Similar to, and being independent of, RANKL, TNFα recruits TNF receptor-associated factors (TRAFs) to sequentially activate transcriptional factors NF-κB p50 and p52, followed by c-Fos, and then NFATc1 to induce OC differentiation. However, induction of OC formation by TNFα alone is very limited, since it also induces many inhibitory proteins, such as TRAF3, p100, IRF8, and RBP-j. TNFα induction of OC differentiation is, however, versatile, and Interleukin-1 or TGFβ1 can enhance TNFα-induced OC formation through a mechanism which is independent of RANKL, TRAF6, and/or NF-κB. However, TNFα polarized macrophages also produce anabolic factors, including insulin such as 6 peptide and Jagged1, to slow down bone loss in the pathological conditions. Thus, the development of novel approaches targeting TNFα signaling should focus on its downstream molecules that do not affect its anabolic effect.


2021 ◽  
Vol 12 ◽  
Author(s):  
Nikolaos Skartsis ◽  
Yani Peng ◽  
Leonardo M. R. Ferreira ◽  
Vinh Nguyen ◽  
Emilie Ronin ◽  
...  

Treg therapies are being tested in clinical trials in transplantation and autoimmune diseases, however, the impact of inflammation on Tregs remains controversial. We challenged human Tregs ex-vivo with pro-inflammatory cytokines IL-6 and TNFα and observed greatly enhanced proliferation stimulated by anti-CD3 and anti-CD28 (aCD3/28) beads or CD28 superagonist (CD28SA). The cytokine-exposed Tregs maintained high expression of FOXP3 and HELIOS, demethylated FOXP3 enhancer, and low IFNγ, IL-4, and IL-17 secretion. Blocking TNF receptor using etanercept or deletion of TNF receptor 2 using CRISPR/Cas9 blunted Treg proliferation and attenuated FOXP3 and HELIOS expression. These results prompted us to consider using CD28SA together with IL-6 and TNFα without aCD3/28 beads (beadless) as an alternative protocol for therapeutic Treg manufacturing. Metabolomics profiling revealed more active glycolysis and oxidative phosphorylation, increased energy production, and higher antioxidant potential during beadless Treg expansion. Finally, beadless expanded Tregs maintained suppressive functions in vitro and in vivo. These results demonstrate that human Tregs positively respond to proinflammatory cytokines with enhanced proliferation without compromising their lineage identity or function. This property can be harnessed for therapeutic Treg manufacturing.


Author(s):  
Jamie Z. Roberts ◽  
Nyree Crawford ◽  
Daniel B. Longley

AbstractCell death pathways have evolved to maintain tissue homoeostasis and eliminate potentially harmful cells from within an organism, such as cells with damaged DNA that could lead to cancer. Apoptosis, known to eliminate cells in a predominantly non-inflammatory manner, is controlled by two main branches, the intrinsic and extrinsic apoptotic pathways. While the intrinsic pathway is regulated by the Bcl-2 family members, the extrinsic pathway is controlled by the Death receptors, members of the tumour necrosis factor (TNF) receptor superfamily. Death receptors can also activate a pro-inflammatory type of cell death, necroptosis, when Caspase-8 is inhibited. Apoptotic pathways are known to be tightly regulated by post-translational modifications, especially by ubiquitination. This review discusses research on ubiquitination-mediated regulation of apoptotic signalling. Additionally, the emerging importance of ubiquitination in regulating necroptosis is discussed.


2021 ◽  
Vol 17 (11) ◽  
Author(s):  
John Nguyen ◽  
Johannes Pettmann ◽  
Philipp Kruger ◽  
Omer Dushek

2021 ◽  
Vol 12 ◽  
Author(s):  
Siliang Man ◽  
Lidong Hu ◽  
Xiaojian Ji ◽  
Yiwen Wang ◽  
Yingpei Ma ◽  
...  

Objective: Concerns exist regarding the potential development of malignancy and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. We assessed the extent to which biologic therapy may increase the risk of malignancy and tuberculosis in patients with SpA by meta-analysis to derive estimates of sparse harmful events occurring in Randomized Controlled Trials (RCTs).Methods: A systematic literature search was conducted in PubMed, EMbase, Web of Science, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating the risk of sparse harmful events of biologic therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto OR for malignancy and tuberculosis in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using Cochrane Risk of Bias tool.Results: In total, 63 studies were included in this meta-analysis, and 83 patients and 7 patients developed malignancy and tuberculosis, respectively. Overall, the risk of malignancy and tuberculosis was increased in SpA patients treated with biologics compared to placebo (malignancy: Peto OR: 2.49, 95%CI: 1.61–3.87, p < 0.001; tuberculosis: Peto OR: 5.98, 95%CI: 1.29–27.76, p = 0.022). Remarkably, compared to placebo, there was higher risk of malignancy for IL-17 inhibitors (Peto OR: 3.68, 95%CI: 1.20–11.30, p = 0.023) and small molecule targeted drugs (Peto OR: 3.08, 95%CI: 1.37–6.90, p = 0.043) in peripheral SpA, and for TNF receptor-Fc fusion protein in axial SpA (Peto OR: 7.18, 95%CI: 1.21–42.69, p = 0.030). Besides, the risk of tuberculosis was higher for anti-TNFα antibody in axial SpA (Peto OR: 6.17, 95%CI: 1.03–37.13, p = 0.046).Conclusion: This meta-analysis showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and small molecule targeted drugs, a slightly increased risk of malignancy in TNF receptor-Fc fusion protein in axial SpA, and increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. These findings need to be validated by studies with larger population and longer follow-up.


2021 ◽  
Vol 22 (19) ◽  
pp. 10724
Author(s):  
Hyoung Moon Kim ◽  
Seyeon Oh ◽  
Jin Young Yang ◽  
Hye Jin Sun ◽  
Miran Jang ◽  
...  

Autophagy is involved in the degradation of melanosomes and the determination of skin color. TLR4 and tumor necrosis factor (TNF) signaling upregulates NF-kB expression, which is involved in the upregulation of mTOR. The activation of mTOR by UV-B exposure results in decreased autophagy, whereas radiofrequency (RF) irradiation decreases TLR4 and TNF receptor (TNFR) expression. We evaluated whether RF decreased skin pigmentation by restoring autophagy by decreasing the expression of TLR4 or TNFR/NF-κB/mTOR in the UV-B-irradiated animal model. UV-B radiation induced the expressions of TNFR, TLR, and NF-κB in the skin, which were all decreased by RF irradiation. RF irradiation also decreased phosphorylated mTOR expression and upregulated autophagy initiation factors such as FIP200, ULK1, ULK2, ATG13, and ATG101 in the UV-B-irradiated skin. Beclin 1 expression and the expression ratio of LC3-I to LC3-II were increased by UV-B/RF irradiation. Furthermore, melanin-containing autophagosomes increased with RF irradiation. Fontana-Masson staining showed that the amount of melanin deposition in the skin was decreased by RF irradiation. This study showed that RF irradiation decreased skin pigmentation by restoring melanosomal autophagy, and that the possible signal pathways which modulate autophagy could be TLR4, TNFR, NF-κB, and mTOR.


Author(s):  
А.В. Малярчиков ◽  
К.Г. Шаповалов

Актуальность. Системный про- и противовоспалительный каскад реакций является одним из патофизиологических компонентов развития критического состояния различного генеза. Поиск биологических маркёров и патогенетических механизмов влияния на макроорганизм систем рецепторов, участвующих в реализации реакций врожденного и адаптивного иммунитета, вследствие повреждения или инфекции, остается актуальным научным направлением. Цель исследования. Оценить активность системы рецепторов TNFRSF7 и TNFRSF9, определив их плазменную концентрацию у больных пневмониями на фоне гриппа A/H1N1. Материалы и методы. Обследовали 85 больных пневмонией на фоне гриппа A/H1N1. Из них 30 пациентов с тяжёлой пневмонией, 55 - с нетяжёлой пневмонией. Методом проточной цитофлуометрии определяли плазменную концентрацию молекул TNFRSF7 и TNFRSF9. Результаты. Установили, что что у больных тяжёлой пневмонией на фоне гриппа A/H1N1 плазменная концентрация рецепторов TNFRSF7 и TNFRSF9 увеличивалась в 1,8 и в 2,3 раза соответственно. Заключение. Увеличение концентрации TNFRSF7 и TNFRSF9 у больных пневмониями на фоне гриппа A/H1N1 свидетельствует о вовлечении в реализацию реакций врожденного и адаптивного иммунитета суперсемейства рецепторов TNF и ассоциировано с тяжестью состояния. Background. Systemic pro- and anti-inflammatory cascades of reactions are pathophysiological components of various critical states. It remains relevant to search for biological markers and pathogenetic mechanisms of effects on the macro-organism of receptor systems involved in innate and adaptive immunity induced by damage or infection. Aim of the study. To evaluate the activity of the TNFRSF7 and TNFRSF9 receptor systems by determining their plasma concentrations in pneumonia patients with influenza A (H1N1). Materials and methods. 85 patients with pneumonia associated with influenza A (H1N1) were examined. Among them, 30 patients had severe pneumonia, and 55 patients had non-severe pneumonia. Plasma levels of TNFRSF7 and TNFRSF9 were measured by flow cytometry. Results. In patients with severe pneumonia and underlying influenza A (H1N1), the plasma concentrations of TNFRSF7 and TNFRSF9 receptors increased 1.8-fold and 2.3-fold, respectively. Conclusion. The significant increase in plasma TNFRSF7 and TNFRSF9 receptors in patients with pneumonia associated with influenza A (H1N1) indicates the involvement of the TNF receptor superfamily in innate and adaptive immunity reactions and is related with severity of the disease.


Sign in / Sign up

Export Citation Format

Share Document