Wound‐associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing

Inflammation is a critical phase in the healing of skin wounds. Excessive inflammation and inflammatory macrophages are known to cause impaired wound closure and outcome. This prompted us to test the role of IL-23 in IL-17 expression and in modulating wound inflammation and macrophage polarization. Full-thickness wounds (4 × 6 mm) were created on the dorsal surface of multiple genetically modified mouse models. Obese diabetic mouse wounds were treated with anti-IL-17A, anti-IL-23, or isotype-matched antibodies. We found IL-23- but not IL-12-deficient mice displayed significantly reduced IL-17 expression in wounds. This was rescued by delivery of recombinant IL-23. IL-23- and IL-17-deficient mice showed a significant increase in noninflammatory macrophages. Obese diabetic mice treated with anti-IL-17A and anti-IL-23p19 blocking antibodies had significantly improved wound reepithelialization. Similarly, IL-17 obese mice had accelerated wound closure, resulting in reduced iNOS expression and inflammatory macrophages while maintaining prohealing CD206 and lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1)-expressing macrophages. This study highlights the importance of the IL-17 pathway in wound closure offering new possibilities of therapeutic intervention in chronic wounds.-Lee, J., Rodero, M. P., Patel, J., Moi, D., Mazzieri, R., Khosrotehrani, K. Interleukin-23 regulates interleukin-17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization.

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“…Wounding was performed as described elsewhere (18). Mice were anesthetized by isoflurane gas inhalation at 2% in 100% O 2 .…”

Section: Methodsmentioning

confidence: 99%

Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization

et al. 2018

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“…Although the macrophage wound‐healing role remains to be completely elucidated, the recent use of genetically modified mice has allowed for a selective and specific depletion of wound macrophages, advancing the functional understanding of these cells and emphasizing their critical role in the beginning and middle of the healing process . Nevertheless, as in all animal studies, translation of findings to humans must be regarded as tentative.…”

Section: The Role Of Macrophages In Wound Healingmentioning

confidence: 99%

Macrophages: A review of their role in wound healing and their therapeutic use

Snyder

Lantis

Kirsner

et al. 2016

Wound Repair Regeneration

190

121

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Macrophages are mononuclear phagocytes established during embryogenesis and derived from the yolk sac or the fetal liver but also recruited from the blood and bone marrow under proliferative inflammatory conditions (such as tissue repair). Most importantly, they take on distinct phenotypes and functions crucial to healing upon localization in the wound. The objective of this review is to summarize recent findings in regard to the cellular mechanisms of macrophages and chronic wounds. Advances in the potential use of macrophage therapy have arisen based, in part, on the fact that early recruitment of macrophages is critical to wound healing. Higher quality evidence is needed to support the use of macrophage therapy for chronic wound types, as is a better understanding of the signaling related to macrophage polarization, activation of macrophages, and their effect of mechanisms of repair. An evaluation of the currently available research on mechanism of action may lead to a better understanding of the signaling processes of the many macrophage phenotypes, as well as their roles and outcomes in wound healing, which could then guide the development and eventual widespread use of macrophage therapies.

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“…They are an important medium for wound healing, tissue remodelling and cytokine secretion. The active inflammation defence is mediated by M1 macrophage, and the wound healing and tissue repair are regulated by M2/M2‐like macrophages .…”

Section: Discussionmentioning

confidence: 99%

“…They are an important medium for wound healing, tissue remodelling and cytokine A B secretion. The active inflammation defence is mediated by M1 macrophage, and the wound healing and tissue repair are regulated by M2/M2-like macrophages (12). Normally, the macrophages increase in number beginning the first day of injury, and the numbers increase with time, not only reaching a peak 2-4 days after the injury, but also reaching 80% of total cells in the granulation tissues on the seventh post-injury day, thus becoming the inflammatory cells that persist for the longest period and are the largest in number (13).…”

Section: Discussionmentioning

confidence: 99%

Application of vacuum sealing drainage to the treatment of seawater‐immersed blast‐injury wounds

Shi

Sun

Cao

et al. 2015

International Wound Journal

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The aims of this study were to observe the effects of vacuum sealing drainage (VSD) with three different negative pressures on the wound healing rate, macrophage count and the expression of hyaluronic acid (HA) as well as its receptor CD44 in seawater-immersed blast-injury wounds (SIBIW) and to determine the optimal negative pressure value. In a minipig SIBIW model, different suction pressures and routine dressing were applied. Histological and immunohistochemical comparisons as well as molecular biology methods were performed to compare the wound healing conditions, macrophage count and the levels of HA and CD44. The wound healing rate of the VSD group was significantly higher than that of the control group, with the -120 mmHg group exhibiting the best effects. The macrophage count of the VSD group was higher than that of the control group. The HA level fluctuation was higher in the VSD group, with the -120 mmHg and the -180 mmHg groups showing the most significant fluctuation (P < 0·05). CD44 was expressed in the full-thickness wound-limbic tissues and was higher in the treatment group than that in the control group, with the -120 mmHg group having the most obvious expression. VSD significantly improved the healing ability and increased the macrophage count and the HA content. It also promoted CD44 expression. -120 mmHg is the optimal negative pressure value.

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Wound‐associated macrophages control collagen 1α2 transcription during the early stages of skin wound healing

Cited by 34 publications

References 18 publications

Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization

Interleukin‐23 regulates interleukin‐17 expression in wounds, and its inhibition accelerates diabetic wound healing through the alteration of macrophage polarization

Macrophages: A review of their role in wound healing and their therapeutic use

Application of vacuum sealing drainage to the treatment of seawater‐immersed blast‐injury wounds

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