- Tripeptide (Lys-Pro-Val)
- Anti-inflammatory
- PepT1 is a di/tripeptide transporter expressed in small intestine and induced in colon during IBD
- Nanomolar concentrations of KPV inhibit activation of NF-kappaB and MAP kinase (MAPK) inflammatory signaling pathways and reduce pro-inflammatory cytokine secretion
- KPV acts via PepT1 expressed in immune and intestinal epithelial cells.
- Melanocortin system
- 5 transmembrane G protein-coupled receptors PLUS 2 endogenous antagonists
- Melanocortin’s comprise adrenocorticotropic hormone (ACTH), a-, b- and y-melanocyte-stimulating hormones
- C-terminal tripeptide derivatives of a-MSH (i.e., KPV) and KdPT possess anti-inflammatory properties
- KPV weakens inflammatory response in colonic epithelium and intestinal immune cells that lead to a reduction in IBD
- Mice were given KPV who had experimental colitis induced by dextran sulfate sodium (DDS) and trinitrobenzene sulfonic acid (TNBS). Index of neutrophilic infiltration myeloperoxidase (MPO) activity was assessed, and the results showed approximately a 50% decrease in MPO activity in the mice treated with oral KPV. This study also led to a belief that KPV has a non-receptor-dependent immunoregulatory effect. Mice who were given the DDS had a decrease in the expression of pro-inflammatory cytokine mRNA levels of IL-6 but did not change the expression of IL-10 mRNA suggesting KPV acts by decreasing pro-inflammatory cytokines instead of increasing anti-inflammatory one.
- Hyaluronic acid lysine-proline-valine nanoparticles (HA-KPV-NPs) can enhance mucosal healing AND regulate inflammatory response with ulcerative colitis.
- Oral HA-KPV-NPs encapsulated in a hydrogel exhibited higher potency for preventing epithelial injury
- Questioning if KPV can be used in other inflammatory diseases i.e., lung inflammation in COVID-19
- KPV effect on MAPK pathway:
- IL-1B induces rapid phosphorylation of ERK1/2, JNK and p38 in Caco2-BBE cells BUT when treated with KPV there was a strong decrease in IL-1B-induced MAPK phosphorylation
Duration of treatment:
As long as it takes to treat the inflammatory process! In our clinical practice we typically extend 3-6 months beyond once we have the clinical symptoms under control.
We have not experienced any contraindications using this small peptide and we have been happy with both oral and subq use for inflammatory disease. We are very encouraged with this new nanoparticle approach and believe this is the potential future of improved treatments for gut dysbiosis!
References:
Dinparastisaleh, Roshan, and Mehdi Mirsaeidi. “Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player.” Pharmaceuticals 14, no. 1 (January 8, 2021): 45. https://doi.org/10.3390/ph14010045.
Dalmasso, Guillaume, Laetitia Charrier-Hisamuddin, Hang Thi Thu Nguyen, Yutao Yan, Shanthi Sitaraman, and Didier Merlin. “PepT1-Mediated Tripeptide KPV Uptake Reduces Intestinal Inflammation.” Gastroenterology 134, no. 1 (January 2008): 166–78. https://doi.org/10.1053/j.gastro.2007.10.026
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