Mechanisms of ivermectin-induced wound healing

Abstract Background Wounds cause structural and functional discontinuity of an organ. Wound healing, therefore, seeks to re-establish the normal morphology and functionality through intertwined stages of hemostasis, inflammation, proliferation, and tissue remodelling. Ivermectin, a macrolide, has been used as an endectoparasiticide in human and veterinary medicine practice for decades. Here, we show that ivermectin exhibits wounding healing activity by mechanisms independent of its well-known antiparasitic activity. This study aimed to evaluate the wound healing property of ivermectin cream using histochemistry and enzyme-linked immunosorbent assay techniques. Results Non-irritant dose of ivermectin cream (0.03–1%) decreased wound macroscopic indices such as exudation, edge edema, hyperemia, and granulation tissue deposition by day 9 compared to day 13 for the vehicle-treated group. This corresponded with a statistically significant wound contraction rate, hydroxyproline deposition, and a decreased time to heal rate. The levels of growth factors TGF-β1 and VEGF were significantly elevated on day 7 but decreased on day 21. This corresponded with changes in cytokines (IL-1α, IL-4, IL-10, and TNF-α) and eicosanoids (LTB4, PGE2, and PGD2) levels on days 7 and 21.. Interestingly, low doses of ivermectin cream (0.03–0.1%) induced wound healing with minimal scarring compared to higher doses of the cream and the positive control, Silver Sulfadiazine. Conclusion Ivermectin promotes wound healing partly through modulation of the inflammatory process and the levels of Transforming Growth Factor-Beta 1 and Vascular Endothelial Growth Factor. Low doses of ivermectin cream have the potential to be used in treating wounds with minimal scar tissue formation.

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Platelet-Released Growth Factors and Platelet-Rich Fibrin Induce Expression of Factors Involved in Extracellular Matrix Organization in Human Keratinocytes

International Journal of Molecular Sciences ◽

10.3390/ijms21124404 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4404

Author(s):

Andreas Bayer ◽

Bernard Wijaya ◽

Lena Möbus ◽

Franziska Rademacher ◽

Meno Rodewald ◽

...

Keyword(s):

Extracellular Matrix ◽

Wound Healing ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Collagen Type ◽

Transforming Growth Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Related Factors ◽

Platelet Rich Fibrin

Platelet-released growth factor (PRGF) is a thrombocyte concentrate lysate which, like its clinically equivalent variations (e.g., Vivostat PRF® (platelet-rich fibrin)), is known to support the healing of chronic and hard-to-heal wounds. However, studies on the effect of PRGF on keratinocytes remain scarce. This study aims to identify genes in keratinocytes that are significantly influenced by PRGF. Therefore, we performed a whole transcriptome and gene ontology (GO) enrichment analysis of PRGF-stimulated human primary keratinocytes. This revealed an increased expression of genes involved in extracellular matrix (ECM) organization. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) analysis confirmed the PRGF-mediated induction of selected ECM-related factors such as transforming growth factor beta-induced protein, fibronectin 1, matrix metalloproteinase-9, transglutaminase 2, fermitin family member 1, collagen type I alpha 1 and collagen type XXII alpha 1. PRGF-induced expression of the above factors was influenced by blockade of the epidermal growth factor receptor (EGFR), a receptor playing a crucial role in wound healing. A differential induction of the investigated factors was also detected in skin explants exposed to PRGF and in experimentally generated in vivo wounds treated with Vivostat PRF®. Together, our study indicates that the induction of ECM-related factors may contribute to the beneficial wound-healing effects of PRGF-based formulations.

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Detection of transforming growth factor-beta in sputum from patients with bronchial asthma by eosinophil survival assay and enzyme-linked immunosorbent assay

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.1996.d01-346.x ◽

1996 ◽

Vol 26 (5) ◽

pp. 557-562 ◽

Cited By ~ 1

Author(s):

T. ADACHI ◽

S. MOTOJIMA ◽

A. HIRATA ◽

T. FUKUDA ◽

N. KIHARA ◽

...

Keyword(s):

Growth Factor ◽

Bronchial Asthma ◽

Immunosorbent Assay ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Eosinophil Survival ◽

Survival Assay ◽

Growth Factor Beta

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Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring

Advances in Wound Care ◽

10.1089/wound.2013.0429 ◽

2013 ◽

Vol 2 (5) ◽

pp. 195-214 ◽

Cited By ~ 120

Author(s):

Kenneth W. Finnson ◽

Sarah McLean ◽

Gianni M. Di Guglielmo ◽

Anie Philip

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Growth Factor Beta

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Transforming growth factor beta 1 dependent regulation of Tenascin-C in radiation impaired wound healing

Radiotherapy and Oncology ◽

10.1016/j.radonc.2004.07.011 ◽

2004 ◽

Vol 72 (3) ◽

pp. 297-303 ◽

Cited By ~ 24

Author(s):

Falk Wehrhan ◽

Franz Rödel ◽

Gerhard G. Grabenbauer ◽

Kerstin Amann ◽

Wolfgang Brückl ◽

...

Keyword(s):

Wound Healing ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Impaired Wound Healing ◽

Tenascin C ◽

Growth Factor Beta

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Induction of Growth Factor Expression is Reduced during Healing of Tympanic Membrane Perforations in Glucocorticoid-Treated Rats

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940211101015 ◽

2002 ◽

Vol 111 (10) ◽

pp. 947-953 ◽

Cited By ~ 16

Author(s):

Shin-Ichi Ishimoto ◽

Toshio Ishibashi

Keyword(s):

Wound Healing ◽

Growth Factors ◽

Growth Factor ◽

Mrna Expression ◽

Messenger Rna ◽

Transforming Growth Factor ◽

Keratinocyte Growth Factor ◽

Treated Group ◽

Transforming Growth Factor Α ◽

Tympanic Membrane Perforations

The participation of growth factors in wound healing of tympanic membranes (TMs) is established. To determine the possible role of these growth factors in normal healing, we examined the regulation of keratinocyte growth factor (KGF), transforming growth factor–α (TGF-α), and basic fibroblast growth factor (bFGF) messenger RNA (mRNA) expression in wounded TMs of glucocorticoid-treated rats; these rats have severe wound healing abnormalities. Induction of KGF, TGF-α, and bFGF mRNA expression after TM injury was significantly reduced in these rats. Moreover, we found that the average number of bromodeoxyundine-positive cells in a glucocorticoid-treated group was significantly lower than that in controls. The data suggest that reduced expression of these genes might be partially responsible for the wound healing defects seen in these animals. These results provide a possible explanation for the beneficial effect of exogenous KGF, TGF-α, or bFGF in treatment of wound healing disorders of the TM.

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Production of monoclonal antibodies that detect Hodgkin's high molecular weight transforming growth factor-beta

Blood ◽

10.1182/blood.v75.12.2434.bloodjournal75122434 ◽

1990 ◽

Vol 75 (12) ◽

pp. 2434-2437

Author(s):

SR Newcom ◽

LH Muth ◽

ET Parker

Keyword(s):

Molecular Weight ◽

Monoclonal Antibodies ◽

Growth Factor ◽

High Molecular Weight ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Antigenic Determinants ◽

Enzyme Linked Immunosorbent Assay ◽

Tgf Beta ◽

Growth Factor Beta

High molecular weight transforming growth factor-beta (TGF beta) is a physiologically active TGF secreted by nodular sclerosing Reed- Sternberg cells. Five monoclonal murine antibodies were prepared that distinguished Hodgkin's TGF beta from platelet-derived TGF beta using an enzyme-linked immunosorbent assay, neutralization of biologic activity, and Western blotting. These monoclonal antibodies directed at unique antigenic determinants (epitopes) of Hodgkin's TGF beta will allow further characterization of the role of Hodgkin's TGF beta in Hodgkin's disease and related entities.

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