Figure 2.

(A) TNFα signalling via a receptor complex comprising CD14 and toll-like receptor 4 (TLR4). Upon LPS binding to this complex, signal transduction via TLR4 leads to the activation of the transcription factor NF-κB. Therefore, IκB is cleared off the molecule. After transcription and translation, trimeric TNFα is inserted into the cell membrane. The TNFα converting enzyme (TACE) cleaves TNFα off the membrane to yield its soluble form (sTNFα). (B) IL-6 signalling via IL-6R and gp130. Only the latter has to be expressed to render the respective cell susceptible to IL-6, because soluble IL-6R can interact with membrane bound gp130. The activation of the receptor complex leads to the activation of different transcription factors, such as STAT1 and STAT3. (C) TNFα mediated effects. Several untoward effects have been implicated into the over-expression of TNFα. See text for details. gp, glycoprotein; IκB, inhibitory κB; IL, interleukin; iNOS, inducible isoform of nitric oxide synthase; LPS, lipopolysaccharide; LV, left ventricular; NF-κB, nuclear factor-κB; R, receptor; s, soluble; STAT, signal transducers and activator of transcription; TACE, TNFα converting enzyme; TNFα, tumour necrosis factor α.