Potential Contribution of the VIP Gene to HS

TIZ emerged as one of the genes with real potential as a candidate for HS. TIZ inhibits TRAF6, a tumour-necrosis-factor- (TNF-) associated factor that is a signal transducer in the TNF receptor superfamily pathway, and also mediates nuclear factor kappa B (NF-kB) and JNK activation in the interleukin-1 receptor/ Toll-like receptor (IL-1R/TLR) signalling pathway. NF-kB together with activator protein 1 are activated in acne lesions with consequent elevated expression of their target gene products, inflammatory cytokines and matrix-degrading metalloproteinases [31]. TRAF6 deficiency in mice illustrates its role in immune and inflammatory response. These mice showed a defect in normal B-cell differentiation, lymph node organogenesis, IL-1 signalling and lipopolysac-charide signalling. The mice, generally, showed features of hypohidrotic ectodermal dysplasia (HED) due to sweat gland, hair and dental abnormalities. This phenotype is not associated with HS but TNF and IL-1 signalling pathways have been implicated in playing a role in the disease. A gain-of-function mutation or dominant negative mutation in the TIZ gene may act in a different manner than a knockout of TRAF6. The effects of such a TIZ mutation might there

TNF, as previously mentioned, activates a number of proinflammatory cytokines including vasoactive intestinal peptide (VIP), which is located within the chromosome 6 candidate region [59]. VIP is a 28-amino-acid regulatory peptide that is widely expressed in the nervous system and other tissues such as lung and skin. It plays a role in a wide variety of functions such as neurotransmission, neuroprotection and is a modulator of growth, survival and differentiation [23]. Other research has shown that VIP can in fact increase the production of inflammatory cytokines TNFa, IL-3, IL-1ß, IL-6, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) [9, 27]. Inflammatory cytokines can stimulate VIP synthesis, which can in turn inhibit these same cytokines in a negative feedback system illustrating its immunoregulatory function. VIP is highly expressed in the skin and is found in the sebaceous gland and sweat gland of the pilosebaceous unit and a mutation in VIP could potentially cause an inflammatory and immune disease such as HS [5, 30]. It is expressed in the appendages involved in HS and is involved in signalling in the immune and inflammatory response. Although these are thought to be coincidental secondary features of HS, they may cause obstruction and an aberrant immune response by activating or inhibiting downstream effectors in these pathways.

Acne Myths Uncovered

Acne Myths Uncovered

What is acne? Certainly, most of us know what it is, simply because we have had to experience it at one time or another in our lives. But, in case a definition is needed, here is a short one.

Get My Free Ebook

Post a comment