Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells
: Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorptio...
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Published in | Experimental dermatology Vol. 14; no. 11; pp. 854 - 859 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK; Malden, USA
Munksgaard International Publishers
01.11.2005
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | : Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorption, are easily metabolized and are immunogenic. Using computational methods, the natural product amygdalin was identified as peptidomimetic of PT. However, amygdalin exhibits a toxic profile due to its cyanide group. To overcome this deleterious effect, we synthesized analogues lacking the cyanide group. Human keratinocytes were treated with PT or with three different peptidomimetics of PT. To study its effects on the expression of HSP‐70, TGF‐β, α‐v integrin, ICAM‐1 and cytokines, we analysed the protein levels by Western blot and ELISA. Our results show that the different peptidomimetics of PT tested exhibit a similar biological behaviour in regard to the overexpression of HSP‐70, TGF‐β and α‐v integrin than the native peptide. TNF‐α is overexpressed by PT and SVT‐03018; between the other two analogs, SVT‐03016 do not produce any significant change in regard to the control, while SVT‐03017 shows only a moderate increase in regard to control. SVT‐03018 provokes a remarkable upregulation of IL‐10, stronger than SVT‐03016, SVT‐03017 and PT. All the other three analogues reduce comparably to the PT, the expression of ICAM‐1 and do not increase the release of proinflammatory cytokines. The results highlighted that the three analogues of amygdalin with the cyanide group removed exhibit the same biological effects of PT. Therefore, they can be considered peptidomimetics, suggesting their possible use in the treatment of psoriasis. |
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Bibliography: | istex:8C72C91D9C359733A67C167B01FF2DA059E67D5B ark:/67375/WNG-QN6PHHKC-8 ArticleID:EXD368 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0906-6705 1600-0625 |
DOI: | 10.1111/j.1600-0625.2005.00368.x |