Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes.
Pincelli. C C; Fantini. F F; Romualdi. P P; Sevignani. C C; Lesa. G G; Benassi. L L; Giannetti. A A
Key Findings
- VIP levels are elevated in psoriatic skin, whereas substance P levels are reduced.
- VIP (full‑length and certain fragments) stimulates the proliferation of human keratinocytes in a dose‑dependent way.
- Substance P does not promote keratinocyte growth and can block the growth‑stimulating effect of VIP.
- The GRF‑1‑29‑derived antagonist (N‑Ac‑Tyr1, D‑Phe2‑GRF‑1‑29‑NH2) inhibits VIP‑driven keratinocyte proliferation.
Practical Outcomes
- For biohackers focused on longevity or performance, this research offers little actionable insight. It mainly shows that GRF‑1‑29 can block a skin‑growth signal, but it does not suggest any health‑optimizing protocol or dosage for the broader community.
Summary
The study looked at two brain‑derived peptides, VIP and substance P, in psoriasis‑affected skin. VIP was higher and substance P lower in lesions, and VIP made skin cells grow while substance P stopped that growth. A short version of the peptide GRF‑1‑29 acted as a blocker of VIP’s effect on the cells.
Abstract
An involvement of neurogenic components in the pathogenesis of psoriatic lesions has been suggested and neuropeptides are thought to play a modulatory role in cutaneous inflammation. In this study, we evaluated the immunoreactivity of the neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the skin of patients with chronic plaque psoriasis, by immunohistochemistry and radioimmunoassay. No differences were observed, by immunohistochemistry, in the expression and localization of VIP and SP between psoriatic and normal skin. Using the radioimmunologic technique on whole skin homogenates, VIP levels were significantly increased in psoriatic lesions as compared to normal skin. By contrast, SP levels were significantly lower in lesional and non-lesional psoriatic skin than in normal skin. In addition, we examined the effect of VIP and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1 nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1 microM) stimulated the proliferation of keratinocytes in a dose-dependent manner, whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not only failed to stimulate keratinocyte growth, but also blocked the VIP-induced stimulation of these cells. The imbalance of cutaneous VIP and SP and their disparate effects on the proliferation of normal human keratinocytes in culture would suggest that these peptides are involved in the pathogenesis of psoriasis and may exert different modulatory activities in the mechanisms underlying the psoriatic lesion.
Study Information
pubmed
1992
10.1111/1523-1747.ep12499846