Key findings
- Uptake experiments with tritiated peptide and cold competition established transport by PepT1 in intestinal epithelial and immune cell lines, and nanomolar concentrations inhibited NF-kappaB and MAP kinase signalling in those cells. [1]
- In bronchial epithelial cells the peptide entered the nucleus, stabilised IkappaB alpha and blocked nuclear translocation of p65RelA through an interaction at the importin alpha binding site, a route the authors separate from melanocortin receptor activation. [2]
- The related four-residue peptide GKPV inhibited TNF-alpha stimulated NF-kappaB reporter activity both as a soluble peptide and while immobilised on beads, which the authors read as a cell surface receptor based mechanism. [3]
- Two recent cell culture papers report reactive oxygen species as the upstream step, with downstream MAPK and NF-kappaB changes in keratinocytes and PPAR gamma and fatty acid synthase changes in a hepatic cell line. [4][5]
Identity and structure
- Related four-residue peptide
- GKPV is residues 10 to 13 of alpha-melanocyte stimulating hormone and carries an extra glycine; one cited paper used GKPV rather than the three-residue peptide [3]
- Transporter in cited work
- Taken into cells by PepT1, the di and tripeptide transporter expressed in intestinal epithelial and immune cells [1]
- Terminal modifications in cited work
- Modified forms appear in the literature under the same name, including H-KPV-NH2 and Ac-KPV-NH2 as well as glycoalkylated lysine analogues [6]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The transport step and the signalling step were established together. Cold peptide competed with a radiolabelled PepT1 substrate and tritiated peptide gave the kinetic characteristics of uptake, and in the same cells nanomolar concentrations inhibited activation of NF-kappaB and MAP kinase pathways and lowered pro-inflammatory cytokine secretion. The authors place PepT1 in both intestinal epithelial and immune cells. [1]
Airway epithelial work describes what happens after entry. The peptide was imported into the nucleus, IkappaB alpha was stabilised, and nuclear translocation of YFP-tagged p65RelA was suppressed. Competition assays pointed to an interaction between the peptide and the importin alpha 3 binding site on p65RelA, possibly blocking armadillo domains 7 and 8. The same paper shows that the melanocortin receptor 3 agonist gamma-MSH reaches a similar endpoint by a different route that does require the receptor. [2]
Where the peptide was held outside the cell the effect persisted. GKPV coupled to polystyrene beads through a polyethylene glycol linker inhibited the TNF-alpha stimulated NF-kappaB reporter in one of two growth conditions, and soluble GKPV and alpha-MSH did the same, which the authors read as evidence for a receptor based rather than purely intracellular mechanism. That paper used the four-residue peptide. [3]
Research findings
In vitro
- System
- Human intestinal epithelial cell lines Caco2-BBE and HT29-Cl.19A and human Jurkat T cells stimulated with pro-inflammatory cytokines
- Measured
- NF-kappaB luciferase reporter activity, Western blot, real time RT-PCR and ELISA for pro-inflammatory cytokines, competition of cold peptide against a radiolabelled PepT1 substrate, and uptake kinetics with tritiated peptide
- Reported
- Nanomolar concentrations inhibited activation of NF-kappaB and MAP kinase signalling and reduced pro-inflammatory cytokine secretion. Uptake proceeded through PepT1 expressed in both the immune and the intestinal epithelial cells. [1]
Preclinical in vivo
- System
- Mice with dextran sodium sulfate induced and trinitrobenzene sulfonic acid induced colitis, the animal arm of the same paper as the cell line work above
- Measured
- Incidence of colitis at the histologic level and pro-inflammatory cytokine messenger RNA expression in the colon
- Reported
- The incidence of colitis fell in both models, with lower pro-inflammatory cytokine expression than in the untreated animals. [1]
In vitro
- System
- Immortalised human bronchial epithelial cells 16HBE14o- stimulated with TNF-alpha or respiratory syncytial virus, with the melanocortin receptor 3 agonist gamma-MSH tested in parallel
- Measured
- NF-kappaB reporter gene activity, matrix metalloproteinase 9 activity, IL8 and eotaxin secretion, nuclear import of the peptide, IkappaB alpha stability, nuclear translocation of YFP-tagged p65RelA, and competition at the importin alpha binding site
- Reported
- Both peptides inhibited NF-kappaB, matrix metalloproteinase 9 activity and IL8 and eotaxin secretion with increasing concentration. The tripeptide effect tracked its nuclear import, IkappaB alpha stabilisation and suppressed p65RelA translocation, with competition indicating an interaction at the importin alpha 3 binding site, while the gamma-MSH effect required melanocortin receptor 3. [2]
In vitro
- System
- HBL cells stably transfected with an NF-kappaB luciferase reporter, exposed to the four-residue peptide GKPV immobilised on polystyrene beads through a polyethylene glycol linker, to soluble GKPV or alpha-MSH, or to beads carrying no peptide
- Measured
- NF-kappaB luciferase activity after stimulation with TNF-alpha, comparing immobilised peptide, soluble peptide and peptide-free beads
- Reported
- Peptide functionalised beads significantly inhibited NF-kappaB luciferase activity against peptide-free beads in one of the two growth conditions tested, and soluble alpha-MSH and GKPV were also confirmed to inhibit the reporter. [3]
In vitro
- System
- The acetylated amidated tripeptide Ac-KPV-NH2 and alpha and epsilon glycoalkylated lysine analogues prepared from H-KPV-NH2, rather than the unmodified tripeptide
- Measured
- Antimicrobial activity of the parent and the analogues under a range of conditions, and stability toward proteolytic enzymes
- Reported
- No antimicrobial activity was found for Ac-KPV-NH2 or for the alpha or epsilon glycoalkylated analogues under any of the conditions tested. The glycoalkylated peptides did show stability toward proteolytic enzymes. [6]
Ex vivo
- System
- Dermatomed human skin mounted in diffusion cells, with iontophoresis, microneedle microporation and their combination
- Measured
- Peptide permeation and skin retention under passive diffusion, microneedle treatment, anodal iontophoresis and the combination, the influence of current strength, peptide concentration and duration, and confocal imaging of fluorescein labelled peptide
- Reported
- Permeation was below the 0.01 microgram per millilitre detection limit under passive diffusion. Microneedle treatment gave 4.4 micrograms per square centimetre per hour, iontophoresis and the combination raised the permeation rate 8 and 35 fold above microneedles alone, and retention rose 5 to 10 fold above passive diffusion. Labelled peptide was imaged beyond 100 micrometres of depth. [7]
In vitro
- System
- Human HaCaT keratinocytes exposed to fine particulate matter, with a three-dimensional reconstructed skin model reported alongside
- Measured
- Cell proliferation and viability, IL-1beta secretion, reactive oxygen species production, ERK and p38 MAPK activation, NF-kappaB, caspase-1 activation and the apoptosis proteins Bax, Bcl-2 and cleaved caspase-3
- Reported
- Particulate matter suppressed proliferation and raised IL-1beta. The peptide restored viability, lowered IL-1beta, inhibited reactive oxygen species production and the ERK and p38 activation downstream of it, reduced the apoptosis associated proteins through NF-kappaB suppression, and blocked reactive oxygen species driven caspase-1 activation. The three-dimensional model showed the same attenuation of inflammatory cell death. [4]
In vitro
- System
- Hepatic epithelial HepG2 cells loaded with oleic acid to build up lipid
- Measured
- Lipid accumulation, fatty acid synthase expression, cytotoxicity, reactive oxygen species generation, ERK activation, AKT and mTORC1 phosphorylation, and phosphorylation of PPAR gamma
- Reported
- Oleic acid raised lipid deposition and fatty acid synthase expression. The peptide attenuated both without cytotoxicity, reduced reactive oxygen species and the ERK activation that followed, lowered AKT and mTORC1 phosphorylation, and changed PPAR gamma phosphorylation, which the authors connect to the normalised fatty acid synthase expression. [5]
Handling for in-vitro work
- Charge in cited work
- Carries a positive charge below pH 7.0, which is why anodal iontophoresis was used in the cited permeation work [7]
- Proteolytic stability
- The unmodified tripeptide is susceptible to enzymatic degradation in the cited work; only the glycoalkylated lysine analogues showed stability toward proteolytic enzymes [6]
- Assay concentrations in cited work
- Signalling effects in intestinal and immune cell lines were seen at nanomolar concentrations in the culture medium [1]
- Storage
- Lyophilized at -20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- One cited paper used the four-residue GKPV and another used acetylated and amidated or glycoalkylated forms, so the terminal chemistry of a supplied lot decides which of the cited results can be compared against it.
- The cited work proposes both a PepT1 dependent intracellular route and a surface based route from immobilised peptide, and does not resolve which dominates in a given cell type.
- Transporter expression is part of the experimental context in the intestinal work, so a cell line without PepT1 is not expected to reproduce those uptake results.
- The keratinocyte and hepatocyte papers both place reactive oxygen species upstream but use different challenges and readouts, and no cited paper compares them directly.
Clinical literature attached to this fragment concerns finished formulations rather than a research material, and is out of scope for this profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0025-1 ↗KPV · 99.50% HPLC2026-09-16
References
- Dalmasso G, Charrier-Hisamuddin L, Nguyen HT, et al. PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology. 2008.
- Land SC 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. International journal of physiology, pathophysiology and pharmacology. 2012.
- Kelly JM, Moir AJ, Carlson K, et al. Immobilized alpha-melanocyte stimulating hormone 10-13 (GKPV) inhibits tumor necrosis factor-alpha stimulated NF-kappaB activity. Peptides. 2006.
- Sung J, Ju SY, Park S, et al. Lysine-Proline-Valine peptide mitigates fine dust-induced keratinocyte apoptosis and inflammation by regulating oxidative stress and modulating the MAPK/NF-κB pathway. Tissue & cell. 2025.
- Lee JY, Lee J, Jung WK, et al. Lysine-proline-valine peptide attenuates hepatic lipid accumulation through ROS-dependent regulation of the PPARγ pathway in HepG2 cells. Cytotechnology. 2026.
- Songok AC, Panta P, Doerrler WT, et al. Structural modification of the tripeptide KPV by reductive "glycoalkylation" of the lysine residue. PloS one. 2018.
- Pawar K, Kolli CS, Rangari VK, et al. Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin. Journal of pharmaceutical sciences. 2017.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.