Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

D’Arpa, Peter; Leung, Kai P.

doi:10.1089/wound.2017.0733

Cited by 59 publications

(49 citation statements)

References 71 publications

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“…Binding of LMW HA to TLR4 on antigen presenting cells also leads to dendritic maturation ( Termeer et al, 2002 ). This signaling cascade can be enhanced by fibroblasts, which further enable the responses to DAMPs and production of IL-6, IL-8, and MCP-1 to escalate the state of inflammation ( Wang et al, 2011 ; D’Arpa and Leung, 2017 ).…”

Section: Role Of the Extracellular Matrix And Hyaluronan In Wound Heamentioning

confidence: 99%

The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing

Singampalli

Balaji

Wang

et al. 2020

Front. Cell Dev. Biol.

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Scar formation is the typical endpoint of postnatal dermal wound healing, which affects more than 100 million individuals annually. Not only do scars cause a functional burden by reducing the biomechanical strength of skin at the site of injury, but they also significantly increase healthcare costs and impose psychosocial challenges. Though the mechanisms that dictate how dermal wounds heal are still not completely understood, they are regulated by extracellular matrix (ECM) remodeling, neovascularization, and inflammatory responses. The cytokine interleukin (IL)-10 has emerged as a key mediator of the pro- to anti-inflammatory transition that counters collagen deposition in scarring. In parallel, the high molecular weight (HMW) glycosaminoglycan hyaluronan (HA) is present in the ECM and acts in concert with IL-10 to block pro-inflammatory signals and attenuate fibrotic responses. Notably, high concentrations of both IL-10 and HMW HA are produced in early gestational fetal skin, which heals scarlessly. Since fibroblasts are responsible for collagen deposition, it is critical to determine how the concerted actions of IL-10 and HA drive their function to potentially control fibrogenesis. Beyond their independent actions, an auto-regulatory IL-10/HA axis may exist to modulate the magnitude of CD4 + effector T lymphocyte activation and enhance T regulatory cell function in order to reduce scarring. This review underscores the pathophysiological impact of the IL-10/HA axis as a multifaceted molecular mechanism to direct primary cell responders and regulators toward either regenerative dermal tissue repair or scarring.

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Section: Role Of the Extracellular Matrix And Hyaluronan In Wound Heamentioning

confidence: 99%

The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing

Singampalli

Balaji

Wang

et al. 2020

Front. Cell Dev. Biol.

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“…We investigated the impact of NV-and IL-MSCs on skin wound healing in vitro. We first developed a wound closure assay in which we intoxicated keratinocytes with a cocktail of stress molecules known to be overexpressed during traumatic skin injuries (D'Arpa and Leung, 2017;Stanojcic et al, 2018). IL-MSCs strongly accelerated the wound closure of intoxicated keratinocytes (P < 0.05) and did so faster than NV-MSCs (P < 0.05, Figure 1a).…”

Section: Il-mscs Support Wound Healing and Epidermal Maturation In Vitromentioning

confidence: 99%

IL-1β–Primed Mesenchymal Stromal Cells Improve Epidermal Substitute Engraftment and Wound Healing via Matrix Metalloproteinases and Transforming Growth Factor-β1

Magne

Dedier²,

Nivet

et al. 2020

Journal of Investigative Dermatology

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Since the 1980s, deep and extensive skin wounds and burns are treated with autologous split-thickness skin grafts, or cultured epidermal autografts, when donor sites are limited. However, the clinical use of cultured epidermal autografts often remains unsatisfactory because of poor engraftment rates, altered wound healing, and reduced skin functionality. In the past few decades, mesenchymal stromal cells (MSCs) have raised much attention because of their anti-inflammatory, protrophic, and pro-remodeling capacities. More specifically, gingival MSCs have been shown to possess enhanced wound healing properties compared with other tissue sources. Growing evidence also indicates that MSC priming could potentiate therapeutic effects in diverse in vitro and in vivo models of skin trauma. In this study, we found that IL-1beprimed gingival MSCs promoted cell migration, dermal-epidermal junction formation, and inflammation reduction in vitro, as well as improved epidermal substitute engraftment in vivo. IL-1beprimed gingival MSCs had different secretory profiles from naive gingival MSCs, characterized by an overexpression of transforming growth factor-b and matrix metalloproteinase (MMP) pathway agonists. Eventually, MMP-1, MMP-9, and transforming growth factor-b1 appeared to be critically involved in IL-1beprimed gingival MSC mechanisms of action.

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“…DAMPs, however, can be generated over a long period of time. Different types of DAMPs, such as heat shock proteins (HSPs), are released under conditions of stress or tissue injury such as traumatic lesions, burns and oxidative stress [11, 28]. The major HSPs that are generated during tissue damage are HSP 47 and 70 [24, 46].…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptors (TLRs) Expression in Contracted Capsules Compared to Uncontracted Capsules

et al. 2019

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Introduction The etiology of capsular contracture after surgical implantation of breast implants remains unclear, but an important role is seen for the immune system. Toll-like receptors are immune receptors recognizing both pathogen-associated molecular patterns and damage-associated molecular patterns. The former are present on bacteria such as Staphylococcus epidermidis (bacteria earlier associated with capsular contracture), and the latter are released after (mechanical) stress. The aim of this study was to investigate the expression of TLRs 1–10 in relation to capsular contracture. Materials and Methods Fifty consecutive breast capsules were collected during implant removal or replacement. The extent of capsular contracture was scored according to the Baker score. A sample specimen (0.5 cm 3 ) was obtained from all tissues. cDNA was synthesized from isolated mRNA from the collected specimens. PCR analyses were conducted to test for cDNA presence and to quantify concentration. TLR1–10 expression was measured for each of the Baker scores separately and compared to all Baker scores. Results Expression of all TLRs in all Baker scores was seen. TLR2 and TLR6 were more often present in contracted samples (Baker 3 or 4) compared to uncontracted samples (Baker 1 or 2) [Baker 2 vs. 3 ( p = 0.034) and Baker 2 vs. 3 ( p = 0.003), respectively]. None of the TLRs displayed a significantly higher expression in contracted capsules compared to uncontracted capsules. Conclusion This study shows that TLR2 and TLR6 are more often expressed in contracted capsules compared to non-contracted capsules however not in higher concentrations. Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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Toll-Like Receptor Signaling in Burn Wound Healing and Scarring

Cited by 59 publications

References 71 publications

The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing

The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing

IL-1β–Primed Mesenchymal Stromal Cells Improve Epidermal Substitute Engraftment and Wound Healing via Matrix Metalloproteinases and Transforming Growth Factor-β1

Toll-Like Receptors (TLRs) Expression in Contracted Capsules Compared to Uncontracted Capsules

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