Wound Healing Is Impaired in MyD88-Deficient Mice

Macedo, Lisa; Pinhal‐Enfield, Grace; Alshits, Vera; Elson, Genie; Cronstein, Bruce N.; Leibovich, Samuel

doi:10.2353/ajpath.2007.061048

Cited by 140 publications

(53 citation statements)

References 94 publications

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“…Although deletion of single TLRs does not affect regeneration, deletion of the common TLR adapter MyD88 or elimination of intestinally-derived TLR ligands in germ-free mice suppresses liver regeneration 58–60 . A contribution of TLR signaling to regeneration is also found in the intestine, where a TLR2/TLR4/MyD88 signaling cascade mediates epithelial regeneration after DSS-mediated injury 53,61 , and in the skin, where lack of MyD88 slows the healing of excisional skin wounds 62 . In the intestine and liver, TLR-MyD88 signaling regulates the expression of mitogenic EGF receptor ligands epiregulin and amphiregulin in non-hematopoietic cells.…”

Section: Tumor Promoting Actions Of Tlrsmentioning

confidence: 99%

The Yin and Yang of Toll-like receptors in cancer

2013

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Recognition of non-self molecular patterns by pattern recognition receptors is a cornerstone of innate immunity. Toll-like receptors (TLRs) exert a key role in recognizing pathogen-associated molecular patterns (PAMPs) but have also been implicated in the recognition of damage-associated molecular patterns (DAMPs). As such, TLRs regulate a wide range of biological responses including inflammatory and immune responses during carcinogenesis. The high expression of TLRs by antigen-presenting cells, including dendritic cells, and their ability to induce anti-tumor mediators such as type I interferon has led to efforts to utilize TLR agonists in tumor therapy in order to convert the often tolerant immune response towards anti-tumor responses. However, TLRs are also increasingly recognized as regulators of tumor-promoting inflammation and promoters of tumor survival signals. Here, we will review in detail the dichotomous role of TLRs in tumor biology, focusing on relevant TLR-dependent pro- and anti-tumor pathways, and discuss clinical applications of TLR-targeted therapies for tumor prevention and treatment.

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Section: Tumor Promoting Actions Of Tlrsmentioning

confidence: 99%

The Yin and Yang of Toll-like receptors in cancer

2013

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“…There is synergy between TLR and A2AR signaling that switches macrophages from an inflammatory to an angiogenic phenotype, which plays a role in wound healing in vivo [54]. The A2AR agonist, NECA, strongly inhibited TNF production in murine macrophages treated with TLR2, -3, -4, -7, or 9 agonists [55].…”

Section: Adenosine In Innate Immunitymentioning

confidence: 99%

Adenosine modulates Toll-like receptor function: basic mechanisms and translational opportunities

Coombs

Belderbos

Gallington

et al. 2011

Expert Review of Anti-infective Therapy

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Adenosine is an endogenous purine metabolite whose concentration in human blood plasma rises from nanomolar to micromolar during stress or hypoxia. Leukocytes express seven-transmembrane adenosine receptors whose engagement modulates Toll-like receptor-mediated cytokine responses, in part via modulation of intracellular cyclic adenosine monophosphate (cAMP). Adenosine congeners are used clinically to treat arrhythmias and apnea of prematurity. Herein we consider the potential of adenosine congeners as innate immune response modifiers to prevent and/or treat infection.

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“…This abilility of the TLR-microbial interaction to confer protection against tissue injury and maintain homeostasis appears to be surprisingly universal and has been shown in various epithelial tissues such as skin (wound healing) [12], intestine [10], lung epithelium [13], liver cells [14], even in other sites of host-microbial interface, e.g., in pancreatic β-cells [11].…”

Section: Mechanisms Of Tissue Integrity and Homeostasismentioning

confidence: 98%

“…The two major discoveries in immunology, the regulatory network and the Toll-like receptor (TLR) system, have fundamentally added to our understanding of the role of commensals and saprophytes in health and disease. The interaction of microbial components with their specific receptors on/in innate immune and other cells is not only beneficial but even necessary for the development and maintenance of epithelial cell homeostasis and integrity, as well as for tissue repair after injury [10][11][12][13][14]. Tissue injury related to prolonged inflammation and the inability of cells to repair such injury and to return to quiescence have been suggested to increase the risk for cancer [15].…”

Section: Introductionmentioning

confidence: 98%

Microbial deprivation, inflammation and cancer

Hertzen

Joensuu

Haahtela

2011

Cancer Metastasis Rev

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Dysregulated immune function is involved in the pathogenesis of many common human diseases. Living in urban, microbe-poor environment may have a profound influence on the immune function and eventually also on carcinogenesis. Unfortunately, few studies have thus far addressed the role of exposure to the environmental microbiota on the risk of cancer. Which mechanisms are broken in individuals prone to develop chronic inflammation in response to exposure that does not cause harm in others? Recent work in immunology has revealed that Th17 cells, a third subset of Th cells, and inflammatory cytokines, particularly IL-23, are closely linked with tumour-associated inflammation. Albeit the precise role of Th17 cells in cancer is still unclear and a matter of debate, accumulating evidence shows that Th17 cells are enriched in a wide range of human tumours, and that these tumour-derived Th17 cells may promote angiogenesis, tumour growth and inflammation. Regulatory T cells, in turn, appear to have counter-regulatory effects on Th17 cells and can inhibit their function. Thus, the regulatory network, induced and strengthened by continuous exposure to environmental microbiota, may play an important role in tumour immunobiology in preventing the establishment of chronic inflammation in its early phases. In addition, the discovery of the Toll-like receptor (TLR) system has brought micro-organisms to new light; continuous signalling via these TLRs and other receptors that sense microbial components is necessary for epithelial cell integrity, tissue repair, and recovery from injury. In this communication, we summarise the epidemiological data of living in environments with diverse microbial exposures and the risk of cancer, and discuss the related immunological mechanisms, focusing on the links between environmental microbiota, the Th17/IL-23 axis and cancer-associated inflammation.

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Wound Healing Is Impaired in MyD88-Deficient Mice

Cited by 140 publications

References 94 publications

The Yin and Yang of Toll-like receptors in cancer

The Yin and Yang of Toll-like receptors in cancer

Adenosine modulates Toll-like receptor function: basic mechanisms and translational opportunities

Microbial deprivation, inflammation and cancer

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