Effect of the LKEKK Peptide on Human Keratinocytes

Impact of Corona Virus

“…We found that the effects of Np5 on various types of cells (human T and B lymphocytes, human Caco-2 and rat IEC-6 intestinal epithelial cells, murine Raw 264.7 macrophage-like cells) are mediated by a cGMP-dependent pathway [9, 13 14]. Moreover, we have shown that Np5 binds with high affinity to human keratinocytes (Kd 2.6 nМ) and increases in a dose-dependent manner the sGC activity [18]. We here investigated the effect of the peptide on the ability of keratinocytes to IL-17A-induced secretion of TNF-α and IL-1α under partial or total absence of the sGC activity.…”

“…Recently we demonstrated the anti-inflammatory activity of Np5 in a model of TNF-induced inflammation in human Caco-2 intestinal epithelial cells in vitro and in a mouse model of dextran sodium sulfate-induced colitis in vivo [17]. Then we examined the anti-inflammatory potential of Np5 using an in vitro model of IL-17A-induced inflammation in normal human keratinocytes [18]. For this, cells were treated with the peptide in the concentration range of 10 1000 nM, and IL-17A (20 ng/mL) was added to induce inflammation.…”

“…Recently we prepared tritium labeled Np5 and established that it binds with high affinity and specificity to normal human epidermal keratinocytes (NHEK) [2]. Furthermore, it was shown that in the concentration range of 50 1000 nМ Np5 increased in a dose-dependent manner the soluble guanylate cyclase activity in NHEK, significantly reduced IL-17A-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1α) and increased the production of the anti-inflammatory cytokine IL-10 by the cells in vitro.…”

Anti-Inflammatory Effect of the Peptide LKEKK

“…Experiments have shown that the peptide LKEKK in the concentration range of 50-1000 nM dose-dependently reduces IL-17A-induced production of three pro-inflammatory cytokines (TNF-α, IL-6, and IL-1α) and simultaneously increases the production of the anti-inflammatory cytokine IL-10. The peptide with the inverted sequence KKEKL tested in parallel was inactive, which indicates the high specificity of the action of the LKEKK peptide [37,38].…”

“…Experiments showed that TM-α 1 and IFN-α 2 competitively inhibited the binding, while the peptide KKEKL was inactive. The inability of the peptide with the inverted sequence to displace [ 3 H]LKEKK from the complex with the receptor indicates a high binding specificity of the labeled peptide [37].…”