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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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IDR-1018 promoted early keratinocyte proliferation in porcine wounds.Representative examples of paraffin embedded, hematoxylin-eosin-stained sections of porcine wounds at day 10 of the study. Sections show enhanced re-epithelialization in the IDR-1018–treated wounds (A: 200 µg/ml and B: 20 µg/ml) compared to LL-37 (200 µg/ml) (C) and PBS (D) treated wounds at wound edge (white arrow).
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pone-0039373-g005: IDR-1018 promoted early keratinocyte proliferation in porcine wounds.Representative examples of paraffin embedded, hematoxylin-eosin-stained sections of porcine wounds at day 10 of the study. Sections show enhanced re-epithelialization in the IDR-1018–treated wounds (A: 200 µg/ml and B: 20 µg/ml) compared to LL-37 (200 µg/ml) (C) and PBS (D) treated wounds at wound edge (white arrow).

Mentions: Hematoxylin-eosin staining demonstrated that both IDR-1018 and LL-37 evenly formed new epithelium evenly including connective tissue papillae. In contrast, wounds treated with PBS showed decreased organization of newly formed epithelium (Fig 5). IDR-1018 treated wounds exhibited advanced, concentration-dependent, re-epithelialization with keratinocytes migrating from the wound edges towards the centre of the wound forming epithelial tongues. LL-37 treatment resulted in reduced re-epithelialization compared to an equal dosage of IDR-1018.


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)

IDR-1018 promoted early keratinocyte proliferation in porcine wounds.Representative examples of paraffin embedded, hematoxylin-eosin-stained sections of porcine wounds at day 10 of the study. Sections show enhanced re-epithelialization in the IDR-1018–treated wounds (A: 200 µg/ml and B: 20 µg/ml) compared to LL-37 (200 µg/ml) (C) and PBS (D) treated wounds at wound edge (white arrow).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0039373-g005: IDR-1018 promoted early keratinocyte proliferation in porcine wounds.Representative examples of paraffin embedded, hematoxylin-eosin-stained sections of porcine wounds at day 10 of the study. Sections show enhanced re-epithelialization in the IDR-1018–treated wounds (A: 200 µg/ml and B: 20 µg/ml) compared to LL-37 (200 µg/ml) (C) and PBS (D) treated wounds at wound edge (white arrow).
Mentions: Hematoxylin-eosin staining demonstrated that both IDR-1018 and LL-37 evenly formed new epithelium evenly including connective tissue papillae. In contrast, wounds treated with PBS showed decreased organization of newly formed epithelium (Fig 5). IDR-1018 treated wounds exhibited advanced, concentration-dependent, re-epithelialization with keratinocytes migrating from the wound edges towards the centre of the wound forming epithelial tongues. LL-37 treatment resulted in reduced re-epithelialization compared to an equal dosage of IDR-1018.

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