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Innate defense regulator peptide 1018 in wound healing and wound infection.

Steinstraesser L, Hirsch T, Schulte M, Kueckelhaus M, Jacobsen F, Mersch EA, Stricker I, Afacan N, Jenssen H, Hancock RE, Kindrachuk J - PLoS ONE (2012)

Bottom Line: 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.However, no significant differences in bacterial colonization were observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. lars.steinstraesser@ruhr-uni-bochum.de

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.

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Assessment of bacterial colonization in S. aureus infected, porcine skin on day 10 after infection.Wounds were treated with the indicated concentrations of IDR-1018 or LL-37 (positive control). PBS served as negative control. Standard deviation was assessed as SEM.
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pone-0039373-g006: Assessment of bacterial colonization in S. aureus infected, porcine skin on day 10 after infection.Wounds were treated with the indicated concentrations of IDR-1018 or LL-37 (positive control). PBS served as negative control. Standard deviation was assessed as SEM.

Mentions: Interestingly, assessment of bacterial colonization in the wound-tissue showed no significant differences between the treatment groups. On day ten post-infection, bacterial quantification revealed 8×105 cfu (colony forming units)/g tissue for the IDR-1018 20 µg/ml treatment group (n = 3; p = 0.4047 cf. PBS-control) and 7×105 cfu/g tissue for the 200 µg/ml group (n = 3; p = 0.2998 cf. PBS-control). In contrast LL-37 application resulted in a colonization of 1.8×106 cfu/g tissue (n = 3; p = 0.5968 cf. PBS-control) while PBS-control (n = 3) itself had 1.3×106 cfu/g tissue; Fig 6).


Innate defense regulator peptide 1018 in wound healing and wound infection.

Steinstraesser L, Hirsch T, Schulte M, Kueckelhaus M, Jacobsen F, Mersch EA, Stricker I, Afacan N, Jenssen H, Hancock RE, Kindrachuk J - PLoS ONE (2012)

Assessment of bacterial colonization in S. aureus infected, porcine skin on day 10 after infection.Wounds were treated with the indicated concentrations of IDR-1018 or LL-37 (positive control). PBS served as negative control. Standard deviation was assessed as SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412849&req=5

pone-0039373-g006: Assessment of bacterial colonization in S. aureus infected, porcine skin on day 10 after infection.Wounds were treated with the indicated concentrations of IDR-1018 or LL-37 (positive control). PBS served as negative control. Standard deviation was assessed as SEM.
Mentions: Interestingly, assessment of bacterial colonization in the wound-tissue showed no significant differences between the treatment groups. On day ten post-infection, bacterial quantification revealed 8×105 cfu (colony forming units)/g tissue for the IDR-1018 20 µg/ml treatment group (n = 3; p = 0.4047 cf. PBS-control) and 7×105 cfu/g tissue for the 200 µg/ml group (n = 3; p = 0.2998 cf. PBS-control). In contrast LL-37 application resulted in a colonization of 1.8×106 cfu/g tissue (n = 3; p = 0.5968 cf. PBS-control) while PBS-control (n = 3) itself had 1.3×106 cfu/g tissue; Fig 6).

Bottom Line: 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.However, no significant differences in bacterial colonization were observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany. lars.steinstraesser@ruhr-uni-bochum.de

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.

Show MeSH
Related in: MedlinePlus