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Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy
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| Zeitschriftentitel: | Experimental Dermatology |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Experimental Dermatology, 17, 2008, 7, S. 630-630 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Böhm, M. Mastrofrancesco, A. Stroszek, E. Kokot, A. Zouboulis, C. C. Luger, T. A. Böhm, M. Mastrofrancesco, A. Stroszek, E. Kokot, A. Zouboulis, C. C. Luger, T. A. |
|---|---|
| author |
Böhm, M. Mastrofrancesco, A. Stroszek, E. Kokot, A. Zouboulis, C. C. Luger, T. A. |
| spellingShingle |
Böhm, M. Mastrofrancesco, A. Stroszek, E. Kokot, A. Zouboulis, C. C. Luger, T. A. Experimental Dermatology Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy Dermatology Molecular Biology Biochemistry |
| author_sort |
böhm, m. |
| spelling |
Böhm, M. Mastrofrancesco, A. Stroszek, E. Kokot, A. Zouboulis, C. C. Luger, T. A. 0906-6705 1600-0625 Wiley Dermatology Molecular Biology Biochemistry http://dx.doi.org/10.1111/j.1600-0625.2008.00742_13.x <jats:p>There is increasing evidence that selected peptide fragments of the neuropeptide alpha‐melanocyte‐stimulating hormone (alpha‐MSH) have preserved immunomodulatory effects in various <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> models. However, until recently, emphasis has been attributed mostly to peptides related to the central pharmacophore of alpha‐MSH (6–9) as well as to peptides homologous to the C‐terminal tripeptide sequence, MSH (11–13). Here we investigated in detail the <jats:italic>in vitro</jats:italic> effects of an alpha MSH (11–13) derivative, K(D)PT, in which the last amino acid valine of alpha‐MSH (11–13) was substituted by threonine and by the D‐enantiomer of proline in position 2. Using the immortalized human sebocyte cell line SZ95 as an <jats:italic>in vitro</jats:italic> model we demonstrate that K(D)PDT has potent antagonistic effects against interleukin (IL)‐induced activation of NF‐kB presumably by inhibiting IkBalpha protein degradation. In contrast IL‐1‐mediated activation of the stress kinase p38 was not affected. The significance of the NF‐kB‐modulatory effect of K(D)PT was highlighted by suppression of IL‐1‐mediated mRNA expression and protein secretion of IL‐6 and IL‐8, two proinflammatory cytokines crucially implicated in the pathogenesis of acne vulgaris. Interestingly, K(D)PT likewise suppressed P. acnes‐induced expression of IL‐6 and IL‐8. Our <jats:italic>in vitro</jats:italic> data are promising towards the therapeutic exploitation of small peptide derivatives of the C‐terminal domain of alpha‐MSH, e.g. K(D)PT, not only for the treatment of acne but also for many other inflammatory skin diseases.</jats:p> Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy Experimental Dermatology |
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10.1111/j.1600-0625.2008.00742_13.x |
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| title |
Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_unstemmed |
Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_full |
Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_fullStr |
Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_full_unstemmed |
Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_short |
Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_sort |
truncated peptide derivates of the c‐terminal domain of alpha‐msh (11–13) – emerging agents for anti‐inflammatory future therapy |
| topic |
Dermatology Molecular Biology Biochemistry |
| url |
http://dx.doi.org/10.1111/j.1600-0625.2008.00742_13.x |
| publishDate |
2008 |
| physical |
630-630 |
| description |
<jats:p>There is increasing evidence that selected peptide fragments of the neuropeptide alpha‐melanocyte‐stimulating hormone (alpha‐MSH) have preserved immunomodulatory effects in various <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> models. However, until recently, emphasis has been attributed mostly to peptides related to the central pharmacophore of alpha‐MSH (6–9) as well as to peptides homologous to the C‐terminal tripeptide sequence, MSH (11–13). Here we investigated in detail the <jats:italic>in vitro</jats:italic> effects of an alpha MSH (11–13) derivative, K(D)PT, in which the last amino acid valine of alpha‐MSH (11–13) was substituted by threonine and by the D‐enantiomer of proline in position 2. Using the immortalized human sebocyte cell line SZ95 as an <jats:italic>in vitro</jats:italic> model we demonstrate that K(D)PDT has potent antagonistic effects against interleukin (IL)‐induced activation of NF‐kB presumably by inhibiting IkBalpha protein degradation. In contrast IL‐1‐mediated activation of the stress kinase p38 was not affected. The significance of the NF‐kB‐modulatory effect of K(D)PT was highlighted by suppression of IL‐1‐mediated mRNA expression and protein secretion of IL‐6 and IL‐8, two proinflammatory cytokines crucially implicated in the pathogenesis of acne vulgaris. Interestingly, K(D)PT likewise suppressed P. acnes‐induced expression of IL‐6 and IL‐8. Our <jats:italic>in vitro</jats:italic> data are promising towards the therapeutic exploitation of small peptide derivatives of the C‐terminal domain of alpha‐MSH, e.g. K(D)PT, not only for the treatment of acne but also for many other inflammatory skin diseases.</jats:p> |
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| author | Böhm, M., Mastrofrancesco, A., Stroszek, E., Kokot, A., Zouboulis, C. C., Luger, T. A. |
| author_facet | Böhm, M., Mastrofrancesco, A., Stroszek, E., Kokot, A., Zouboulis, C. C., Luger, T. A., Böhm, M., Mastrofrancesco, A., Stroszek, E., Kokot, A., Zouboulis, C. C., Luger, T. A. |
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| description | <jats:p>There is increasing evidence that selected peptide fragments of the neuropeptide alpha‐melanocyte‐stimulating hormone (alpha‐MSH) have preserved immunomodulatory effects in various <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> models. However, until recently, emphasis has been attributed mostly to peptides related to the central pharmacophore of alpha‐MSH (6–9) as well as to peptides homologous to the C‐terminal tripeptide sequence, MSH (11–13). Here we investigated in detail the <jats:italic>in vitro</jats:italic> effects of an alpha MSH (11–13) derivative, K(D)PT, in which the last amino acid valine of alpha‐MSH (11–13) was substituted by threonine and by the D‐enantiomer of proline in position 2. Using the immortalized human sebocyte cell line SZ95 as an <jats:italic>in vitro</jats:italic> model we demonstrate that K(D)PDT has potent antagonistic effects against interleukin (IL)‐induced activation of NF‐kB presumably by inhibiting IkBalpha protein degradation. In contrast IL‐1‐mediated activation of the stress kinase p38 was not affected. The significance of the NF‐kB‐modulatory effect of K(D)PT was highlighted by suppression of IL‐1‐mediated mRNA expression and protein secretion of IL‐6 and IL‐8, two proinflammatory cytokines crucially implicated in the pathogenesis of acne vulgaris. Interestingly, K(D)PT likewise suppressed P. acnes‐induced expression of IL‐6 and IL‐8. Our <jats:italic>in vitro</jats:italic> data are promising towards the therapeutic exploitation of small peptide derivatives of the C‐terminal domain of alpha‐MSH, e.g. K(D)PT, not only for the treatment of acne but also for many other inflammatory skin diseases.</jats:p> |
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| imprint_str_mv | Wiley, 2008 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
| issn | 0906-6705, 1600-0625 |
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| spelling | Böhm, M. Mastrofrancesco, A. Stroszek, E. Kokot, A. Zouboulis, C. C. Luger, T. A. 0906-6705 1600-0625 Wiley Dermatology Molecular Biology Biochemistry http://dx.doi.org/10.1111/j.1600-0625.2008.00742_13.x <jats:p>There is increasing evidence that selected peptide fragments of the neuropeptide alpha‐melanocyte‐stimulating hormone (alpha‐MSH) have preserved immunomodulatory effects in various <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> models. However, until recently, emphasis has been attributed mostly to peptides related to the central pharmacophore of alpha‐MSH (6–9) as well as to peptides homologous to the C‐terminal tripeptide sequence, MSH (11–13). Here we investigated in detail the <jats:italic>in vitro</jats:italic> effects of an alpha MSH (11–13) derivative, K(D)PT, in which the last amino acid valine of alpha‐MSH (11–13) was substituted by threonine and by the D‐enantiomer of proline in position 2. Using the immortalized human sebocyte cell line SZ95 as an <jats:italic>in vitro</jats:italic> model we demonstrate that K(D)PDT has potent antagonistic effects against interleukin (IL)‐induced activation of NF‐kB presumably by inhibiting IkBalpha protein degradation. In contrast IL‐1‐mediated activation of the stress kinase p38 was not affected. The significance of the NF‐kB‐modulatory effect of K(D)PT was highlighted by suppression of IL‐1‐mediated mRNA expression and protein secretion of IL‐6 and IL‐8, two proinflammatory cytokines crucially implicated in the pathogenesis of acne vulgaris. Interestingly, K(D)PT likewise suppressed P. acnes‐induced expression of IL‐6 and IL‐8. Our <jats:italic>in vitro</jats:italic> data are promising towards the therapeutic exploitation of small peptide derivatives of the C‐terminal domain of alpha‐MSH, e.g. K(D)PT, not only for the treatment of acne but also for many other inflammatory skin diseases.</jats:p> Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy Experimental Dermatology |
| spellingShingle | Böhm, M., Mastrofrancesco, A., Stroszek, E., Kokot, A., Zouboulis, C. C., Luger, T. A., Experimental Dermatology, Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy, Dermatology, Molecular Biology, Biochemistry |
| title | Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_full | Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_fullStr | Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_full_unstemmed | Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_short | Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_sort | truncated peptide derivates of the c‐terminal domain of alpha‐msh (11–13) – emerging agents for anti‐inflammatory future therapy |
| title_unstemmed | Truncated peptide derivates of the C‐terminal domain of alpha‐MSH (11–13) – emerging agents for anti‐inflammatory future therapy |
| topic | Dermatology, Molecular Biology, Biochemistry |
| url | http://dx.doi.org/10.1111/j.1600-0625.2008.00742_13.x |