KPV

DESCRIPTION:
KPV (Lysine-Proline-Valine) is a C-terminal tripeptide fragment of α-melanocyte stimulating hormone (αMSH). α-MSH stimulates the production and release of melanin by melanocytes in skin and hair, acting through melanocortin 1 receptor. Several studies have previously shown that KPV has decreased inflammation and tumorigenesis in the body.

The KPV anti-inflammatory effect is PepT1-mediated in intestinal epithelial and immune cells. PepT1 is an oligopeptide transporter that is overexpressed in the in the colonic epithelial cells of chronic ulcerative colitis, which can deliver KPV into cytosol in the intestine. The tripeptide, KPV has significant antimicrobial and anti-inflammatory properties especially in those with psoriasis. Psoriasis is a chronic autoimmune condition which causes the rapid build-up of skin cells and is usually treated using hydrocortisone. In people with psoriasis, KPV has shown to limit symptoms of the condition including itchiness, dryness, redness, peeling, and more. Therefore, KPV could be used for an extended period of time without risking the unwanted complications of long term steroid therapy. KPV is a promising, therapeutic treatment for inflammatory bowel disease (IBD) and colon cancer.

CLINICAL RESEARCH:
Alpha-Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry, Anti Inflammatory and Protective Effects in Vitro and in Vivo, and Future Perspectives for the Treatment of Immune- Mediated Inflammatory Diseases Alpha-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over the last few years have provided evidence that Alpha -MSH has potent protective and anti-inflammatory effects. These effects can be elicited via centrally expressed melanocortin receptors that orchestrate descending neuro-genic anti-inflammatory pathways. Alpha-MSH can also exert anti-inflammatory and protective effects on cells of the immune system and on peripheral nonimmune cell types expressing melanocortin receptors. At the molecular level, Alpha-MSH affects various pathways implicated in regulation of inflammation and protection, i.e., nuclear factor-B activation, expression of adhesion molecules and chemokine receptors, production of pro-inflammatory cytokines and mediators, IL-10 synthesis, T cell proliferation and activity, inflammatory cell migration, expression of anti-oxidative enzymes, and apoptosis.

The anti-inflammatory effects of -MSH have been validated in animal models of experimentally induced fever; irritant and allergic contact dermatitis, vasculitis, and fibrosis; ocular, gastrointestinal, brain, and allergic airway inflammation; and arthritis, but also in models of organ injury. One obstacle limiting the use of alpha-MSH in inflammatory disorders is its pigmentary effect. Due to its preserved anti-inflammatory effect but lack of pigmentary action, the C-terminal tripeptide of -MSH, KPV, has been delineated as an alternative for anti-inflammatory therapy.

KdPT, a derivative of KPV corresponding to amino acids 193–195 of IL-1, is also emerging as a tripeptide with anti-inflammatory effects. The physicochemical properties and expected low costs of production render both agents suitable for the future treatment of immune-mediated inflammatory skin and bowel disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation, and arthritis.

Endocr Rev. 2008 Aug;29(5):581-602. doi: 10.1210/er.2007-0027. Epub 2008 Jul 8. Brzoska T1, Luger TA, Maaser C, Abels C, Böhm M.