Soluble tumor necrosis factor (TNF) receptor-1 induces apoptosis via reverse TNF signaling and autocrine transforming growth factor-β1

被引：89

作者：

Waetzig, GH

Rosenstiel, P

Arlt, A

Till, A

Bräutigam, K

Schäfer, H

Rose-John, S

Seegert, D

Schreiber, S

机构：

[1] Schleswig Holstein Univ Med Ctr, Inst Clin Mol Biol, D-24105 Kiel, Germany

[2] Schleswig Holstein Univ Med Ctr, Lab Mol Gastroenterol & Hepatol, Dept Med 1, D-24105 Kiel, Germany

[3] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany

[4] Conaris Res Inst AG, D-24118 Kiel, Germany

来源：

FASEB JOURNAL | 2004年 / 18卷 / 13期

关键词：

anti-inflammatory agents; autoimmune diseases; inflammation; mitogen-activated protein kinases; signal transduction;

D O I：

10.1096/fj.04-2073fje

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a central role in inflammatory disorders. Transmembrane TNF-alpha and its two receptors are cleaved by the proteinase TNF-alpha converting enzyme (TACE), resulting in appreciable serum levels of soluble TNF-alpha and soluble TNF-alpha receptors (sTNFR1 and -2). The only known functions of sTNFR1 are to antagonize and buffer circulating TNF-alpha. Here, we present evidence that sTNFR1 exerts immunoregulatory functions by induction of apoptosis in monocytes through reverse signaling via transmembrane TNF-alpha. sTNFR1-induced apoptosis is independent of death receptor pathways but depends on autocrine transforming growth factor (TGF)-beta1 signaling through the mitogen-activated protein kinase p38alpha. This novel mechanism has implications for understanding the physiological role of sTNFR1 and for TNF-alpha-blocking therapies of autoimmune diseases.

引用

页码：91 / +

页数：19

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