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Effect of the LKEKK Peptide on Human Keratinocytes

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Abstract

The LKEKK peptide (Np5) corresponding to the 16–20 sequence of thymosin-α1 (TM-α1) and to the 131–135 sequence of interferon-α2 (IFN-α2) and its [3H]Np5 analog were synthesized. [3H]Np5 was found to bond to human keratinocytes with high affinity and specificity (Kd 2.6 nM). Np5 dose-dependently decreased the inerleukin-17A-induced production of inflammatory cytokines (TNF-α, IL-6, and IL-1α) by keratinocytes in a concentration range from 50 to 1000 nM and increased a production of the anti-inflammatory IL-10 cytokine in vitro. The peptide effect was shown to be mediated through an activation of soluble guanylate cyclase.

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REFERENCES

  1. Breitkreutz, D., Mirancea, N., and Nischt, R., Histochem. Cell. Biol., 2009, vol. 132, pp. 1–10. https://doi.org/10.1007/s00418-009-0586

    Article  CAS  PubMed  Google Scholar 

  2. Guilloteau, K., Paris, I., Pedretti, N., Boniface, K., Juchaux, F., Huguier, V., Guillet, G., Bernard, F.-X., Lecron, J.-C., and Morel, F., J. Immunol., 2010, vol. 184, pp. 5263–5270. https://doi.org/10.4049/jimmunol.0902464

    Article  CAS  PubMed  Google Scholar 

  3. Robeony, H., Petit-Paris, I., Garnier, J., Barrault, C., Pedretti, N., Guilloteau, K., Jegou, J-F., Guillet, G., Huguier, V., Lecron, J-C., Bernard, F-X., and Morel, F., PLoS One, 2014, vol. 9, e101937. https://doi.org/10.1371/journal.pone.0101937

    Article  Google Scholar 

  4. Navolotskaya, E.V., Zinchenko, D.V., Zolotarev, Y.A., Kolobov, A.A., and Lipkin, V.M., Biochemistry (Moscow), vol. 81, pp. 871–875. https://doi.org/10.1134/S0006297916080071

  5. Navolotskaya, E.V., Sadovnikov, V.B., Zinchenko, D.V., Lipkin, V.M., and Zav’yalov, V.P., Int. Immunopharmacol., 2017, vol. 50, pp. 279–282. https://doi.org/10.1016/j.intimp.2017.07.011

    Article  CAS  PubMed  Google Scholar 

  6. Navolotskaya, E.V., Sadovnikov, V.B., Zinchenko, D.V., Vladimirov, V.I., Zolotarev, Y.A., and Kolobov, A.A., Russ. J. Bioorg. Chem., 2016, vol. 42, pp. 479–483. https://doi.org/10.1134/S1068162016050137

    Article  CAS  Google Scholar 

  7. Navolotskaya, E.V., Sadovnikov, V.B., Zinchenko, D.V., Vladimirov, V.I., and Zolotarev, Y.A., Russ. J. Bioorg. Chem., 2017, vol. 43, pp. 673–677. https://doi.org/10.1134/S1068162017060115

    Article  CAS  Google Scholar 

  8. Navolotskaya, E.V., Sadovnikov, V.B., Zinchenko, D.V., Vladimirov, V.I., Zolotarev, Y.A., and Lipkin, V.M., Russ. J. Bioorg. Chem., 2018, vol. 44, pp. 403–407. https://doi.org/10.1134/S1068162018030123

    Article  CAS  Google Scholar 

  9. Navolotskaya, E.V., Sadovnikov, V.B., Lipkin, V.M., and Zav’yalov, V.P., Toxicol. In Vitro, 2018, vol. 47, pp. 269–273. https://doi.org/10.1016/j.tiv.2017.12.010

    Article  CAS  PubMed  Google Scholar 

  10. Navolotskaya, E.V., Sadovnikov, V.B., Zinchenko, D.V., Vladimirov, V.I., Zolotarev, Y.A., Lipkin, V.M., and Murashev, A.N., Russ. J. Bioorg. Chem., 2019, vol. 45, pp. 122–128. https://doi.org/10.1134/S1068162019020092

    Article  CAS  Google Scholar 

  11. Cuatrecasas, P., Biochemistry, 1973, vol. 12, pp. 3558–3566.

    Article  CAS  Google Scholar 

  12. Holmgren, J., Lonnroth, I., and Svennerholm, L., Infect. Immun., 1973, vol. 8, pp. 208–214.

    Article  CAS  Google Scholar 

  13. Navolotskayaa, E.V., Sadovnikov, V.B., Lipkin, V.M., and Zav’yalov, V.P., J. Clin. Exp. Immunol., 2019, vol. 4, pp. 1–6. https://doi.org/10.33140/JCEI.04.04.03

    Article  Google Scholar 

  14. Feelisch, M., Kotsonis, P., Siebe, J., Clement, B., and Schmidt, H.H., Mol. Pharmacol., 1999, vol. 56, pp. 243–253. https://doi.org/10.1124/mol.56.2.243

    Article  CAS  PubMed  Google Scholar 

  15. Chorachoo, J., Lambert, S., Furnholm, T., Roberts, L., Reingold, L., Auepemkiate, S., Voravuthikunchai, S.P., and Johnston, A., PLoS One, 2018, vol. 13. e0205340. https://doi.org/10.1371/journal.pone.0205340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zolotarev, Y.A., Dadayan, A.K., Bocharov, E.V., Borisov, Y.A., Vaskovsky, B.V., Dorokhova, E.M., and Myasoedov, N.F., Amino Acids, 2003, vol. 24, pp. 325–333. https://doi.org/10.1007/s00726-002-0404-7

    Article  CAS  PubMed  Google Scholar 

  17. Pennock, B.E., Anal. Biochem., 1973, vol. 56, pp. 306–309.

    Article  CAS  Google Scholar 

  18. Cheng, Y.C. and Prusoff, W., Biochem. Pharmacol., 1973, vol. 22, pp. 3099–3108.

    Article  CAS  Google Scholar 

  19. Schultz, G. and Buhme, E., Methods of Enzymatic Analysis, Weinheim, Germany: Verlag Chemie, 1984, pp. 379–389.

    Google Scholar 

  20. Southam, E., Curr. Protoc. Toxicol., 2001, vol. 10, p. 10.5. https://doi.org/10.1002/0471140856.tx1005s04

  21. Lowry, O.H., Rosebbrough, N.J., Farr, O.L., and Randal, R.J., J. Biol. Chem., 1951, vol. 193, pp. 265–275.

    CAS  PubMed  Google Scholar 

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Funding

This study was supported by the Program for Basic Research of the Presidium of the Russian Academy of Sciences (Molecular and Cellular Biology), project no. III-12 (a project director was the corresponding member of the Russian Academy of Sciences, V.M. Lipkin).

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Authors and Affiliations

  1. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Pushchino Branch, Russian Academy of Sciences, 142290, Pushchino, Moscow oblast, Russia

    E. V. Navolotskaya, V. B. Sadovnikov, D. V. Zinchenko & A. N. Murashev

  2. Institute of Molecular Genetics, Russian Academy of Sciences, 123182, Moscow, Russia

    Y. A. Zolotarev

  3. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia

    V. M. Lipkin

Authors
  1. E. V. Navolotskaya
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  2. V. B. Sadovnikov
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  3. D. V. Zinchenko
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  4. Y. A. Zolotarev
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  5. V. M. Lipkin
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  6. A. N. Murashev
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Corresponding author

Correspondence to E. V. Navolotskaya.

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COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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The authors declare that they have no conflicts of interest.

Additional information

Translated by L. Onoprienko

Abbreviations: CT-B, B-subunit of choleraic toxin; cGMP, cyclic guanosine-3',5'-monophosphate; DSS, dextran sodium sulfate; IFN, interferon; iNOS, inducible NO-synthase; LPS, lipopolysaccharide; ODQ, (1H-[1,2,4]oxadiazolo[4,3-α]quinoxalyn-1-one; pGC, membrane-bond guanylate cyclase; sGC, soluble guanylate cyclase; TM-α1, thymosin-α1.

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Navolotskaya, E.V., Sadovnikov, V.B., Zinchenko, D.V. et al. Effect of the LKEKK Peptide on Human Keratinocytes. Russ J Bioorg Chem 46, 1038–1043 (2020). https://doi.org/10.1134/S1068162020060229

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  • DOI: https://doi.org/10.1134/S1068162020060229

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