The Met-196 → Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) Affects TNF-α-induced Apoptosis by Impaired NF-κB Signaling and Target Gene Expression

Till, Andreas; Rosenstiel, Philip; Krippner‐Heidenreich, Anja; Mascheretti-Croucher, Silvia; Croucher, Peter J.P.; Schäfer, Heiner; Scheurich, Peter; Seegert, Dirk; Schreiber, Stefan

doi:10.1074/jbc.m411541200

Cited by 80 publications

(59 citation statements)

References 58 publications

(44 reference statements)

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“…Both INF and ETA are able to reduce STAT3 phosphorylation to a similar degree in cultured T cells taken from patients with CD. It may well be the neutralization of sTNF that may be important in decreasing STAT3 signaling as sTNF acts in an autocrine fashion to regulate STAT3 [49].…”

Section: Effect On Intracellular Signalingmentioning

confidence: 99%

TNFα blockade in human diseases: Mechanisms and future directions

Wong

Ziring

Korin

et al. 2008

Clinical Immunology

257

162

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Tumor necrosis factor-alpha (TNFα) antagonists have shown remarkable efficacy in a variety of immune-mediated inflammatory diseases (IMIDs). Therapeutic scope and limitations of these agents are reviewed in a recently published article in the Journal. In spite of their therapeutic popularity, little is known about their modes of action in vivo and factors that limit their scope of therapeutic use. Intriguingly, while all TNFα antagonists including blocking antibodies and soluble receptors are effective in certain IMIDs, only anti-TNFα antibodies are effective in other IMIDs. Early efforts at understanding how TNFα antagonists act in IMIDs centered on their ability to neutralize soluble TNFα or to block TNF receptors from binding to their ligands. Subsequent studies suggested a role of complement-mediated lysis or antibody-dependent cell cytotoxicity in their therapeutic effects. More recent models postulate that TNFα blockers may act by affecting intracellular signaling, with the end result being a hastened cell cycle arrest, apoptosis, suppression of cytokine production, or improved Treg cell function. TNFα antagonists can also modulate the functions of myofibroblasts and osteoclasts, which might explain how TNFα antagonists reduce tissue damage in chronic IMIDs. Focusing on the human therapeutic experience, this analytical review will review the biology of mechanisms of action, the limiting factors contributing to disease restriction in therapeutic efficacy, and the mechanism and frequency of treatment-limiting adverse responses of TNFα antagonists. It is hoped that the overview will address the needs of clinicians to decide on optimal use, spur clinical innovation, and incite translational researchers to set priorities for in vivo human investigations.

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Section: Effect On Intracellular Signalingmentioning

confidence: 99%

TNFα blockade in human diseases: Mechanisms and future directions

Wong

Ziring

Korin

et al. 2008

Clinical Immunology

257

162

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“…We previously showed that a nonsynonymous coding SNP, rs1061622 (Met196Arg), significantly alters TNFR2-mediated NF-kB activation and target gene expression (20). Moreover, haplotypes in the 39untranslated region (UTR) have been reported to affect TNFR2 expression by influencing messenger ribonucleic acid (mRNA) decay rate (21).…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

“…The functionally relevant TNFRSF1B polymorphisms rs1061622, rs1061624, rs5030792, and rs3397 (20,21,28) were genotyped in the SAC population. All markers were in Hardy-Weinberg equilibrium in the control group.…”

Section: Analysis Of Tnfrsf1b Snps In Sacmentioning

confidence: 99%

A Functional Haplotype in the 3′Untranslated Region ofTNFRSF1BIs Associated with Tuberculosis in Two African Populations

Möller¹,

Flachsbart²,

Till³

et al. 2010

Am J Respir Crit Care Med

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“…The (CA) n repeat has been found to be associated with essential hypertension, hypercholesterolemia, coronary artery disease, familial combined hyperlipidemia and diabetic neuropathy (Glenn et al 2000;Benjafield et al 2001a, b;Geurts et al 2000). M196R is postulated to affect the proteolytic cleavage of the membrane bound TNFR2 to soluble form, TNF binding and/or TNF induced apoptosis by impaired NF-jB signaling (Stark et al 2003;Till et al 2005). Also, a haplotype including rs3397 in 3 0 UTR which alters TNFR2 stability and activity is associated with insulin resistance in young diabetic subjects (Puga et al 2005;Fernandez-Real et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Association analysis of TNFRSF1B polymorphisms with type 2 diabetes and its related traits in North India

Tabassum

Chavali

Ghosh

et al. 2008

HUGO J

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Inflammation plays a crucial role in the pathogenesis of type 2 diabetes and various lines of evidences suggest an important contribution of type 2 receptor for TNFa (TNFR2), a mediator of inflammatory responses. Though genetic association of TNFRSF1B (encoding TNFR2) polymorphisms have been investigated in various studies, their involvement is not clear because of inconsistent findings. Because of high susceptibility of Indian population to type 2 diabetes and its complications, we evaluated the association of TNFRSF1B polymorphismsrs1061622 (M196R; exon6) and rs3397 (3 0 UTR) and (CA) n repeat (intron 4) in 1,852 subjects including 1,040 cases and 812 controls with type 2 diabetes and its associated peripheral neuropathy and hypertension in North Indians of Indo-European ethnicity. The allelic and genotypic distributions of these polymorphisms were comparable among healthy control vs. type 2 diabetes, peripheral neuropathy vs. non-neuropathy and hypertensive vs. normotensive groups. (CA) n polymorphism has been shown to be associated with diabetic neuropathy in Caucasians, however, this could not be replicated in our study (P = 0.27). None of the polymorphisms were found to influence the 14 anthropometric and biochemical traits related to type 2 diabetes studied here. Thus, we conclude that TNFRSF1B is not a major contributing factor to the genetic risk of type 2 diabetes, its associated peripheral neuropathy and hypertension and related metabolic traits in North Indians.

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The Met-196 → Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) Affects TNF-α-induced Apoptosis by Impaired NF-κB Signaling and Target Gene Expression

Abstract: Tumor necrosis factor-␣ (TNF-␣

Cited by 80 publications

References 58 publications

TNFα blockade in human diseases: Mechanisms and future directions

TNFα blockade in human diseases: Mechanisms and future directions

A Functional Haplotype in the 3′Untranslated Region ofTNFRSF1BIs Associated with Tuberculosis in Two African Populations

Association analysis of TNFRSF1B polymorphisms with type 2 diabetes and its related traits in North India

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