VIP and the potent analog, stearyl‐Nle¹⁷‐VIP, induce proliferation of keratinocytes

Abstract

Vasoactive intestinal polypeptide (VIP) exhibits effects on cell proliferation. Here, VIP, as well as the related peptide, pituitary adenylate cyclase activating peptide (PACAP), promoted human keratinocyte division. Stearyl-Nle 17 -VIP (SNV) was identified as a superior mitogen for the keratinocytic cell line, HaCaT, both in potency (fM^nM concentrations) and efficacy. Reverse transcription-polymerase chain reaction detected in keratinocytes only PACAP mRNA and the relevant type 1 (VPAC 1 R) and type 2 (VPAC 2 R) receptors, while VIP and the third receptor (PAC 1 ) transcripts were absent. Upon serum deprivation of HaCaT, the VPAC 1 R mRNA was apparently increased, while the VPAC 2 R transcript remained constant. Incubation of HaCaT with VIP or SNV increased nitric oxide and cGMP formation. In contrast to VIP, SNV did not augment cAMP. Thus, the paracrine VIP, and autocrine PACAP, related pathways leading to keratinocyte proliferation may involve VPAC 1 R/VPAC 2 R and nitric oxide/cGMP production. ß

Epidermal growth factor and thrombin induced proliferation of immortalized human keratinocytes is coupled to the synthesis of Egr‐1, a zinc finger transcriptional regulator

“…We conclude that both EGF and thrombin function as mitogens for HaCaT cells. In contrast to previous published reports [Sung et al, 1999;Granoth et al, 2000], we did not observe an effect of vasoactive intestinal polypeptide on HaCaT cell proliferation (data not shown).…”

The Role of Neuromediators and Innervation in Cutaneous Wound Healing

“…It is postulated that C-fibres release PACAP in response to neuronal activation which in turn leads vasodilatation and extravasation. PACAP is involved in cutaneous inflammation by releasing histamine from mast cells and it also promotes human keratinocyte proliferation (66).…”

The Significance of Vasoactive Intestinal Peptide in Immunomodulation

“…The VPAC 1 antagonist usually employed was PG 97-269 (Gourlet et al, 1997b). Two lipophilic compounds, the VIP agonist stearyl-norleucine 17 VIP and the antagonist stearylnorleucine 17 neurotensin-VIP hybrid (Gozes et al, 1995;Moody et al, 2002), have been used in immune cells (Delgado et al, 1998;Granoth et al, 2000). The combined used of these analogs could discriminate between pure VPAC 1 and VPAC 2 effects, whereas the relatively contribution of VPAC 1-2 and PAC 1 is more difficult to ascertain.…”