Tumor Necrosis Factor and Regulatory T Cells

CD4⁺CD25⁺FoxP3⁺ regulatory T (Treg) cells play major roles in the maintenance of immune homeostasis. In this review, we comprehensively describe the relationship between tumor necrosis factor (TNF) and Treg cells, focusing on the effects of TNF on Treg cells and on TNF-producing Treg cells. Contradictory results have been reported for the effect of TNF on the suppressive activity of Treg cells. In patients with rheumatoid arthritis, TNF has been shown to reduce the suppressive activity of Treg cells. Meanwhile, however, TNF has also been reported to maintain the suppressive activity of Treg cells via a TNFR2-mediated mechanism. In addition, Treg cells have been found to acquire the ability to produce TNF under inflammatory conditions, such as acute viral hepatitis. These TNF-producing Treg cells exhibit T helper 17-like features and hold significance in various human diseases.

TNFR 2 M196R Polymorphism and Acne Vulgaris in Han Chinese: A Case-control Study / 华中科技大学学报（医学）（英德文版）

In this case-control study,the relationship between M196R(676 T→G)variant in exon6 of tumor necrosis factor receptor type 2(TNFR2)gene and genetic susceptibility of ache vulgaris in Han Chinese was investigated.A total of 93 acne vulgaris patients and 90 healthy subjects from Han Chinese ethnic group were enrolled in this study.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique was adopted to analyze the single nucleotide polymorphisms(SNPs)of TNFR2 M 196R gene,and to examine the association between ache vulgaris and the polymorphisms in TNFR2 M196R gene.The relationship between different genotypcs and the susceptibility of acne vulgaris was analyzed.The results showed that there was significant differencein the frequency of the genotype M/R+R/R in the TNFR2 M196R genetic polymorphisms between acne vulgaris patients and healthy controls(X2=4.343; P=0.037; OR=1.899; 95% CI: 1.036-3.445);and there was significant difference in the allele(R)frequency between acne vulgaris patients and healthy controls(X2=5.588; P=0.018; OR=1.838; 95% CI: 1.105-3.057).It was concluded that the high frequency of 196R allele in the functional M196R polymorphism of TNFR2 is a risk factor for acne vulgaris in Han Chinese.

Expressions of TNFR1,TNFR2 and TRAF2 in laryngeal squamous carcinoma / 吉林大学学报(医学版)

0.05),and TRAF2 was related to the tumor grade only(P

Receptor and Intracellular Signaling Mechanisms Involved in TNF?-induced Expression of Heme Oxygenase-1 in Endothelial Cells / 医学研究杂志

Objective To investigate the receptor involved in the TNF?induced HO-1 expression and the related signal transduction mechanisms in the brain microvessel endothelial cells.Methods TNF? receptor 1(TNFR1)knockout murine brain microvessel endothelial cells(BMVECs)in vitro culture were stimulated respectively by TNF?(5ng/ml).After 24 hours,the level of HO-1 gene mRNA were detected by semi-quantitative RT-PCR,the effect of TNF?on JNK 、ERK or transcription factor AP-1 were analyzed by Western blot,while ERK inhibitor(PD98059)or JNK inhibitor(SP600125)were used.Results Exposure of wild-type BMVECs and TNFR1(p55)knockout BMVECs [BVEC/TNF-RI(-/-)] to TNF?(5ng/ml,24 h)caused a marked increase in HO-1 mRNA expression.Furthermore,TNF? stimulation also lead to the activation of JNK,ERK and the transcription factor AP-1 in the BVEC/TNF-RI(-/-),However,incubation with the JNK inhibitor SP600125 but not the ERK inhibitor PD98095 attenuated the TNF?-induction of HO-1 in the BVEC/TNF-RI(-/-).Conclusions TNFR2 and JNK activation but not TNFR1 might be essential for mediating the TNF?-induction of the HO-1 in the endothelial cells.

TNFalpha and TNFR2 Immunohistochemistry During Ovarian Follicular Development and Atresia in the Rat / 대한해부학회지

Tumor necrosis factor alpha (TNFalpha) is an intraovarian cytokine that may play a role in ovarian development and function. Identification of ovarian TNFalpha receptors provides support for establishing a role of TNFalpha in ovarian development and function. TNFalpha exerts its effects by binding to either TNF receptor 1 or 2 (TNFR1 or TNFR2). When TNFalpha binds with TNFR2, expression of survival genes is up-regulated, resulting in proliferation of granulosa cells. In the present study, the authors identified the changes in localization of TNFalpha and the expression of TNFR2 in granulosa cells during follicular atresia in rat ovaries. In healthy follicles, intense signals for TNFalpha and TNFR2 were found in the outer surface of the granulosa layer, where many proliferating cells and no apoptotic cells were observed. In atretic follicles, decreased expression of TNFalpha and TNFR2 was observed in the granulosa layer, where many apoptotic cells were seen. These findings suggested that TNFalpha acts as a survival factor in granulosa cells during follicular atresia in rat ovaries.

Differential Expression, Shedding, Cytokine Regulation and Function of TNFR1 and TNFR2 in Human Fetal Astrocytes

Tumor necrosis factor (TNF) -alpha induces pleiotropic cellular effects through a 55kDa, type 1 receptor (TNFR1) and a 75kDa type 2 receptor (TNFR2). Moreover, it participates in the pathogenesis of several CNS diseases, including demyelinating diseases. TNF- receptors are differentially expressed and are regulated in many cell types. However, data regarding the TNF-alpha receptor expression and regulation in human astrocytes is limited to date. We investigated TNF-alpha receptor expression, its regulation by cytokines, and its functional role in primary cultured human fetal astrocytes, which are the most abundant cellular population in the central nervous system and are known to be immunologically active. In this study, astrocytes were found to constitutively and predominantly transcribe, translate and shed TNFR1 rather than TNFR2, but TNFR2 expression was increased by adding TNF-alpha, IL-1, and IFN-gamma, but not by adding LPS. To determine the functional roles of TNFR1 and TNFR2 on TNF induction, we investigated NF-kappaB activation and TNF-alpha induction after neutralizing TNFR1 and TNFR2 by an antibody treatment. We found that NF-kappaB activation and TNF-alpha induction are blocked by TNFR1 neutralizing antibody treatments.