KPV

Inhibition of cellular and systemic inflammation cues in human bronchial epithelial cells by melanocortin-related peptides: mechanism of KPV action and a role for MC3R agonists.

Land SC., International Journal of Physiology, Pathophysiology and Pharmacology, 2012;4(2):59-73

published

• In immortalised human bronchial epithelial cells (16HBE14o-) stimulated with TNFα or respiratory syncytial virus, KPV produced a concentration-dependent inhibition of NF-κB reporter activity, matrix metalloproteinase-9 activity and IL-8 and eotaxin secretion. The KPV effect was associated with the peptide's own nuclear import, stabilisation of IκBα and suppressed nuclear translocation of YFP-tagged p65RelA, and competition assays indicated an interaction between KPV and the importin-α3 binding site on p65RelA.
• In the same cells, the comparison peptide γ-MSH required the melanocortin-3 receptor for its effect while the KPV effect did not, which the author presents as two separate routes to suppressing NF-κB signalling in this epithelium.

Anti-Candida activity of alpha-melanocyte-stimulating hormone (alpha-MSH) peptides.

Rauch I, Holzmeister S, Kofler B., Journal of Leukocyte Biology, 2009;85(3):371-372; author reply 373

published (letter; comment on J Leukoc Biol 2000;67(2):233-9)

Material identity not established. This is a letter about alpha-MSH peptides, published as a comment on the antimicrobial study above. Its abstract names alpha-MSH for the assays it ran and does not state separately whether the tripeptide itself was retested, so it is recorded here as a challenge to the antimicrobial finding rather than as a study of this tripeptide.

• A letter in the same journal reports microplate-based growth-inhibition assays on Candida albicans in which no growth-inhibiting effect was observed; on repeating the originally published assay with different C. albicans strains, the authors report detecting only a mild growth-inhibiting effect at 100 µM. The letter was published with a reply from the original authors, which this project has not read.

alpha-Melanocyte-stimulating hormone, MSH 11-13 KPV and adrenocorticotropic hormone signalling in human keratinocyte cells.

Elliott RJ, Szabo M, Wagner MJ, Kemp EH, MacNeil S, Haycock JW., Journal of Investigative Dermatology, 2004;122(4):1010-1019

published

• No elevation of cyclic AMP was detected in HaCaT cells or in normal human keratinocytes in response to α-MSH, KPV or ACTH peptides, although the anti-inflammatory action of α-MSH had been assumed to be cyclic-AMP dependent.
• Rapid, acute rises in intracellular calcium were observed in HaCaT keratinocytes in response to α-MSH, KPV, KP-D-V and ACTH across 10⁻¹⁵ to 10⁻⁷ M, but only in the presence of PIA, an adenosine agonist that inhibits the cyclic AMP pathway. In Chinese hamster ovary cells stably transfected with the melanocortin-1 receptor, the authors report that α-MSH and the KPV peptides — their term, covering both KPV and KP-D-V — elevated intracellular calcium.

Antimicrobial effects of alpha-MSH peptides.

Cutuli M, Cristiani S, Lipton JM, Catania A., Journal of Leukocyte Biology, 2000;67(2):233-239

published; comment and author reply, J Leukoc Biol 2009;85(3):371-2

Material identity not established. This study tested alpha-MSH (1-13) and its C-terminal tripeptide KPV together, and its abstract reports the antimicrobial results for 'alpha-MSH peptides' as a group. Which part of each result belongs to the tripeptide by itself is not established by the abstract.

• Reports that α-MSH (1-13) and its C-terminal tripeptide KPV, tested together as 'α-MSH peptides', significantly inhibited Staphylococcus aureus colony formation and reduced the viability and germ-tube formation of Candida albicans, over a broad concentration range including the picomolar. Cellular cAMP was significantly higher in the yeast after exposure and the adenylyl cyclase inhibitor dideoxyadenosine partly reversed the killing, which the authors read as cAMP involvement. The peptides did not lower killing of either organism by human neutrophils.

PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.

Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, Yan Y, Sitaraman S, Merlin D., Gastroenterology, 2008;134(1):166-178

published

• In human intestinal epithelial cell lines (Caco2-BBE, HT29-Cl.19A) and human T cells (Jurkat) stimulated with pro-inflammatory cytokines, nanomolar concentrations of KPV inhibited activation of NF-κB and of MAP kinase signalling and lowered pro-inflammatory cytokine secretion, measured by NF-κB luciferase reporter, Western blot, real-time RT-PCR and ELISA.
• Uptake experiments using unlabelled KPV as a competitor for a radiolabelled PepT1 substrate, and tritiated KPV to measure uptake kinetics, led the authors to report that the tripeptide is transported into cells by PepT1, a di/tripeptide transporter expressed in the immune and intestinal epithelial cells studied.
• In mice with colitis induced by dextran sodium sulfate and by TNBS, KPV added to drinking water lowered the incidence of colitis, assessed histologically and by pro-inflammatory cytokine mRNA expression. The abstract gives no per-group figures.

Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.

Kannengiesser K, Maaser C, Heidemann J, Luegering A, Ross M, Brzoska T, Böhm M, Luger TA, Domschke W, Kucharzik T., Inflammatory Bowel Diseases, 2008;14(3):324-331

published

• Examined the tripeptide in two mouse models of intestinal inflammation — dextran sodium sulfate colitis and CD45RB-high transfer colitis — following the course by body-weight change, colon histology and myeloperoxidase activity. In the dextran sodium sulfate model the authors report earlier recovery, significantly greater regain of body weight, significantly fewer inflammatory infiltrates on histology and significantly lower myeloperoxidase activity in colonic tissue; in the transfer model they report recovery, regain of body weight and fewer inflammatory changes on histology. The abstract reports no numeric values or p-values for any of these.
• In mice expressing a non-functional melanocortin-1 receptor (MC1Re/e) given dextran sodium sulfate, the authors report that all animals in the KPV group survived, and conclude that the effects seem to be at least partly independent of melanocortin-1 receptor signalling.