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Fig. 1 | Clinical Epigenetics

Fig. 1

From: Transcriptional modulation by VIP: a rational target against inflammatory disease

Fig. 1

Transcription of TNF-α genes by NFκB following stimulation of innate immune cells by lipopolysaccharide (LPS) or cytokines. 1 LPS in fluids is bound by lipopolsaccharide binding protein (LBP); 2 LPS/LBP complexes bind to CD14 receptor; 3 CD14 receptor stimulates TLR4 via an accessory protein (MD2); 4 activation of MyD88 induces a biochemical cascade which (via phosphorylation) activates cytosolic enzymes; 5a including interleukin-1 receptor associated kinase (IRAK), tumour necrosis factor receptor associated factor (TRAF) and Inhibitory κB kinase (IKK); 5b shows that ligation of cytokine with cytokine receptor may have the same effect and activation of cytosolic enzymes can act as a convergence point whereby the effect of LPS on transcriptional regulation is potentiated by cytokine. 6 Phosphorylation and activation of IKK stimulates ubiquitination of NFκB which allows nuclear translocation of NFκB; 7 NFκB binds to NFκB promoter sequences on TNF-α gene; 8 newly synthesised TNF-α is released from the cell to mediate immunity

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