MicroRNA-146a alleviates chronic skin inflammation in atopic dermatitis through suppression of innate immune responses in keratinocytes

Rebane, Ana; Runnel, Toomas; Aab, Alar; Maslovskaja, Julia; Rückert, Beate; Zimmermann, Maya; Plaas, Mario; Kärner, Jaanika; Treis, Angela; Pihlap, Maire; Haljasorg, Uku; Hermann, Helen; Nagy, Nikoletta; Kemény, Lajos; Erm, Triin; Kingo, Külli; Li, Mei; Boldin, Mark; Akdiş, Cezmi A.

doi:10.1016/j.jaci.2014.05.022

Cited by 166 publications

(170 citation statements)

References 60 publications

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“…miR-146a controls nuclear factor B-dependent inflammatory responses in keratinocytes and chronic skin inflammation in atopic dermatitis (19). miRNAs regulate mast cell development (20) and eosinophil differentiation and function (21).…”

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confidence: 99%

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells

Kwon

Kim

Eom

et al. 2015

Journal of Biological Chemistry

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Background:The molecular mechanism of COX-2-mediated allergic inflammation remains unknown. Results: miR-26a/-26b target COX-2 and regulate allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells. Conclusion:The miR-26a/-26b-COX-2-MIP-2 loop regulates a positive feedback between allergic inflammation and tumor metastasis. Significance: The miR-26a/-26b-COX-2-MIP-2 loop can be employed for the development of anti-allergy and anti-cancer drugs.

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mentioning

confidence: 99%

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells

Kwon

Kim

Eom

et al. 2015

Journal of Biological Chemistry

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“…[24][25][26] As shown in Figure 1a and e-h and the left-most panel of Figure 1d, topical administration of MC903 on the ears for 14 days induced tissue swelling, epidermal thickening, and the infiltration of eosinophils and basophils into the dermal layer. Strikingly, topical application of the NOD2/TLR2 ligands together with the AD-inducing agent MC903 further deteriorated the AD-like symptoms, including enhanced ear swelling (Figure 1a-c), more extensive epidermal thickening (Figure 1d and e), and the presence of a larger number of eosinophils in the dermal layer ( Figure 1g).…”

Section: Topical Application Of Nod2/tlr2 Ligands Induced Exacerbatiomentioning

confidence: 88%

“…[24][25][26] A total of 2 nmol of MC903 (Sigma-Aldrich Corp, St. Louis, MO, USA), which is a Th2-related AD-like skin inflammation-inducing compound, was topically applied in 5 mL of ethanol to the ears of the mice every other day for 14 days (days 0-14, eight times in total). [24][25][26] Ear thickness was measured using a dial thickness gauge (Model G, Peacock, OZAKI MFG. CO., LTD, Tokyo, Japan) and recorded every other day for 16 days.…”

Section: Ad Mouse Modelmentioning

confidence: 99%

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

et al. 2015

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The skin of patients with atopic dermatitis (AD) has a unique predisposition for colonization by Staphylococcus aureus (S. aureus), which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll-like receptor 2 (TLR2) ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions. Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway by which S. aureus contributes to the pathophysiology of AD. Cellular & Molecular Immunology

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“…Taken together, these data suggest that strains of CGN associated with a healthy status induce potentially beneficial immune outcomes related to activation of select vitamin D pathway and innate immunity markers as well as potential enhancement of barrier function. (27,28) and involves TSLP (29), CCL5, and CCL8 (30). Parameters affected by the MC903 model include visual redness, ear thickness, and induction of serum IgE (31).…”

Section: Cgn From Hv Induce Select Markers Of Innate Immunity In Humansmentioning

confidence: 99%

Transplantation of human skin microbiota in models of atopic dermatitis

Myles¹

2017

J Bacteriol Parasitol

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MicroRNA-146a alleviates chronic skin inflammation in atopic dermatitis through suppression of innate immune responses in keratinocytes

Cited by 166 publications

References 60 publications

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells

MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

Transplantation of human skin microbiota in models of atopic dermatitis

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