Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection

Lars Steinstraesser, Tobias Hirsch, Matthias Schulte, Maximilian Kueckelhaus, Frank Jacobsen, Evgeniija A. Mersch, Ingo Stricker, Nicole Afacan, Håvard Jenssen, Robert E. W. Hancock, Jason Kindrachuck

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.
    OriginalsprogEngelsk
    TidsskriftP L o S One
    Vol/bind7
    Udgave nummer8
    ISSN1932-6203
    DOI
    StatusUdgivet - 2012

    Bibliografisk note

    Artikel nr. e39373

    Citer dette

    Steinstraesser, L., Hirsch, T., Schulte, M., Kueckelhaus, M., Jacobsen, F., Mersch, E. A., ... Kindrachuck, J. (2012). Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection. P L o S One, 7(8). https://doi.org/10.1371/journal.pone.0039373
    Steinstraesser, Lars ; Hirsch, Tobias ; Schulte, Matthias ; Kueckelhaus, Maximilian ; Jacobsen, Frank ; Mersch, Evgeniija A. ; Stricker, Ingo ; Afacan, Nicole ; Jenssen, Håvard ; Hancock, Robert E. W. ; Kindrachuck, Jason. / Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection. I: P L o S One. 2012 ; Bind 7, Nr. 8.
    @article{d07f8a6fffa34ee8a7e04d25594e7b94,
    title = "Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection",
    abstract = "Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.",
    author = "Lars Steinstraesser and Tobias Hirsch and Matthias Schulte and Maximilian Kueckelhaus and Frank Jacobsen and Mersch, {Evgeniija A.} and Ingo Stricker and Nicole Afacan and H{\aa}vard Jenssen and Hancock, {Robert E. W.} and Jason Kindrachuck",
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    doi = "10.1371/journal.pone.0039373",
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    volume = "7",
    journal = "P L o S One",
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    Steinstraesser, L, Hirsch, T, Schulte, M, Kueckelhaus, M, Jacobsen, F, Mersch, EA, Stricker, I, Afacan, N, Jenssen, H, Hancock, REW & Kindrachuck, J 2012, 'Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection', P L o S One, bind 7, nr. 8. https://doi.org/10.1371/journal.pone.0039373

    Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection. / Steinstraesser, Lars ; Hirsch, Tobias; Schulte, Matthias; Kueckelhaus, Maximilian; Jacobsen, Frank; Mersch, Evgeniija A.; Stricker, Ingo; Afacan, Nicole; Jenssen, Håvard; Hancock, Robert E. W.; Kindrachuck, Jason.

    I: P L o S One, Bind 7, Nr. 8, 2012.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection

    AU - Steinstraesser, Lars

    AU - Hirsch, Tobias

    AU - Schulte, Matthias

    AU - Kueckelhaus, Maximilian

    AU - Jacobsen, Frank

    AU - Mersch, Evgeniija A.

    AU - Stricker, Ingo

    AU - Afacan, Nicole

    AU - Jenssen, Håvard

    AU - Hancock, Robert E. W.

    AU - Kindrachuck, Jason

    N1 - Artikel nr. e39373

    PY - 2012

    Y1 - 2012

    N2 - Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

    AB - Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

    U2 - 10.1371/journal.pone.0039373

    DO - 10.1371/journal.pone.0039373

    M3 - Journal article

    VL - 7

    JO - P L o S One

    JF - P L o S One

    SN - 1932-6203

    IS - 8

    ER -

    Steinstraesser L, Hirsch T, Schulte M, Kueckelhaus M, Jacobsen F, Mersch EA et al. Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection. P L o S One. 2012;7(8). https://doi.org/10.1371/journal.pone.0039373