Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.

Mackay, Fabienne; Loetscher, Hansruedi; Stueber, Dietrich; Gehr, Gisela; Lesslauer, Werner

doi:10.1084/jem.177.5.1277

Cited by 362 publications

(217 citation statements)

References 71 publications

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“…Hence, our data provide evidence that ICAM-1 expression in the liver is exclusively under the control of TNFR1. These findings corroborate previous findings showing that in other cell systems and tissues, TNF-inducible adhesion molecule expression including ICAM-1 and VCAM-1 is mediated by TNFR1 (35,36). The observation that Con A-treated TNFR Ϫ/Ϫ mice express high levels of adhesion molecules, although TNF-induced expression of adhesion molecules in the liver is under control of TNFR1 suggest the involvement of other endothelium activating cytokines such as IL-1, IL-12, or IFN-␥ (37,38).…”

Section: Discussionsupporting

confidence: 82%

TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis

Wolf

Hallmann

Sass

et al. 2001

The Journal of Immunology

108

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TNF-α has been clearly identified as central mediator of T cell activation-induced acute hepatic injury in mice, e.g., Con A hepatitis. In this model, liver injury depends on both TNFRs, i.e., the 55-kDa TNFR1 as well as the 75-kDa TNFR2. We show in this report that the hepatic TNFRs are not transcriptionally regulated, but are regulated by receptor shedding. TNF directly mediates hepatocellular death by activation of TNFR1 but also induces the expression of inflammatory proteins, such as cytokines and adhesion molecules. Here we provide evidence that resistance of TNFR1−/− and TNFR2−/− mice against Con A hepatitis is not due to an impaired production of the central mediators TNF and IFN-γ. Con A injection results in a massive induction of ICAM-1, VCAM-1, and E-selectin in the liver. Lack of either one of both TNFRs did not change adhesion molecule expression in the livers of Con A-treated mice, presumably reflecting the fact that other endothelial cell-activating cytokines up-regulated adhesion molecule expression. However, treatment of TNFR1−/− and TNFR2−/− mice with murine rTNF revealed a predominant role for TNFR1 for the induction of hepatic adhesion molecule expression. Pretreatment with blocking Abs against E- and P-selectin or of ICAM−/− mice with anti-VCAM-1 Abs failed to prevent Con A hepatitis, although accumulation of the critical cell population, i.e., CD4+ T cells was significantly inhibited. Hence, up-regulation of adhesion molecules during acute hepatitis unlikely contributes to organ injury but rather represents a defense mechanism.

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Section: Discussionsupporting

confidence: 82%

TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis

Wolf

Hallmann

Sass

et al. 2001

The Journal of Immunology

108

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“…TNF-α has been shown in animal models to induce pathological features associated with COPD, such as an inflammatory cell infiltrate into the lungs, pulmonary fibrosis and emphysema [62,63]. It enhances neutrophil chemotaxis and migration by inducing the expression of chemokine interleukin 8 (IL-8) and upregulating endothelial adhesion molecules [64,65]. In vivo, elevated levels of TNF-α have been demonstrated in peripheral blood, bronchial biopsies, induced sputum and BALF of patients with stable COPD compared with control subjects [66][67][68][69][70].…”

Section: Role Of Tnf-α In Asthma and Copdmentioning

confidence: 99%

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

Matera

Calzetta

Cazzola

2010

Pulmonary Pharmacology & Therapeutics

118

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Tumor necrosis factor (TNF)-α, a pleiotropic cytokine that exerts a variety of effects, such as growth promotion, growth inhibition, angiogenesis, cytotoxicity, inflammation, and immunomodulation, has been implicated in several inflammatory conditions. It plays a significant role in many inflammatory diseases of lung. Given that there is significant literature supporting the pathobiologic role of TNF-α in asthma, mainly in severe refractory asthma, and COPD, TNF-α inhibitors (infliximab, golimumab and etanercept) are now regarded as potential new medications in asthma and COPD management. The studies reported in literature indicate that TNF-α inhibitors are effective in a relatively small subgroup of patients with severe asthma, possibly defined by an increased TNF axis, but they seem to be ineffective in COPD, although an observational study demonstrated that TNF-α inhibitors were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. These findings require a smart approach because there is still good reason to target TNF-α, perhaps in a more carefully selected patient group. TNF-α treatment should therefore not be thrown out, or abandoned. Indeed, since severe asthma and COPD are heterogeneous diseases that have characteristics that occur with different phenotypes remained poorly characterized and little known about the underlying pathobiology contributing to them, it is likely that definition of these phenotypes and choice of the right outcome measure will allow us to understand which kind of patients can benefit from TNF-α inhibitors.

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“…TNF activation of EC is mostly dependent on TNFR1, although there is evidence that TNFR2 may participate in signaling at suboptimal TNF concentrations, perhaps through ligand passing to TNFR1 (Mackay et al, 1993;Slowik et al, 1993;Tartaglia et al, 1993). Of relevance to the "ligand passing" hypothesis, the two receptors reside largely in different cellular compartments, with TNFR1 predominantly localized to the Golgi apparatus and minimally expressed on the cell surface, and TNFR2 almost exclusively localized to the plasma membrane (Bradley et al, 1995).…”

mentioning

confidence: 99%

The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization

Gaeta

Johnson

Kluger

et al. 2000

Laboratory Investigation

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SUMMARY:TNF signals are mediated through two different receptors, TNFR1 and TNFR2. In endothelial cells, TNFR1 is predominantly localized in the Golgi apparatus and TNFR2 on the plasma membrane. To investigate structural features responsible for the disparate localization, endothelial cells were transfected with epitope-tagged or green fluorescent protein-fused wild type and mutant receptor molecules. Wild type receptors recapitulated the distribution of endogenous receptors. Deletions of the entire TNFR1 intracellular domain or of the C-terminal death domain (TNFR1 ϪDD ) allowed expression of the receptor on the plasma membrane. However, addition of the death domain to the C-terminus of TNFR2 (TNFR2 ϩDD ) did not lead to Golgi-retention of this chimeric receptor. Overexpressed TNFR1, TNFR2, and TNFR2 ϩDD increased basal expression of a cotransfected NF-B-dependent promotor-reporter gene. Overexpressed TNFR1 ϪDD did not activate NF-B but acted as a ligand-specific dominant negative inhibitor of TNF actions. Unexpectedly, TNF responses were also inhibited by overexpressed TNFR1 and TNFR2 ϩDD , but not TNFR2. We conclude that the death domain of TNFR1 is required for retention of TNFR1 in the Golgi apparatus but is not sufficient to direct Golgi retention of a TNFR2 ϩDD chimera, and that overexpressed receptors that contain the death domain (TNFR1 and TNFR2 ϩDD ) spontaneously activate NF-B while inhibiting TNF responses. (Lab Invest 2000, 80:1185-1194.

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Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.

Cited by 362 publications

References 71 publications

TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis

TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis

TNF-α inhibitors in asthma and COPD: We must not throw the baby out with the bath water

The Death Domain of Tumor Necrosis Factor Receptor 1 Is Necessary but Not Sufficient for Golgi Retention of the Receptor and Mediates Receptor Desensitization

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