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Role of macrophages in the pathogenesis of atopic dermatitis.

ABSTRACT: Atopic dermatitis (AD) is one of the most common and most intensively studied chronic inflammatory skin diseases. Several cofactors, such as an impaired skin barrier function, modifications of the immune system, and a complex genetic background, direct the course of AD. Within this complex network, macrophages play a pivotal role in enhanced susceptibility to cutaneous infections and act as central connecting components in the pathogenesis of AD on the cellular level. In AD, macrophages are known to accumulate in acutely and chronically inflamed skin. During the early and short inflammatory phase, macrophages exert proinflammatory functions like antigen-presenting phagocytosis and the production of inflammatory cytokines and growth factors that facilitate the resolution of inflammation. However, persistence of pro-inflammatory activity and altered function of macrophages result in the development of chronic inflammatory diseases such as AD. The exact mechanism of macrophages activation in these processes is not yet completely understood. Further studies should be performed to clarify the dysregulated mechanism of macrophages activation in AD, and this would allow us to target these cells with versatile functions for therapeutic purpose and improve and control the disease. In this paper, we highlight the new findings on dysregulated function of macrophages and the importance of these cells in the pathogenesis of AD in general and the contribution of these cells in enhanced susceptibility against microbial infections in particular.

SUBMITTER: Kasraie S

PROVIDER: S-EPMC3603294 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Role of macrophages in the pathogenesis of atopic dermatitis.

Kasraie Sadaf S Werfel Thomas T

Mediators of inflammation 20130304

Atopic dermatitis (AD) is one of the most common and most intensively studied chronic inflammatory skin diseases. Several cofactors, such as an impaired skin barrier function, modifications of the immune system, and a complex genetic background, direct the course of AD. Within this complex network, macrophages play a pivotal role in enhanced susceptibility to cutaneous infections and act as central connecting components in the pathogenesis of AD on the cellular level. In AD, macrophages are know ...[more]

PMID: 23533313

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Project description:Previous studies have demonstrated that microRNA (miR)‑146a is involved in the inflammatory response of atopic dermatitis (AD). The aim of the present study was to investigate the expression of miR‑146a in the serum of patients with AD and in skin lesions of AD animal models. In addition, we aimed to predict and verify the target genes of miR‑146a. miR‑146a expression was measured in AD patient serum via reverse transcription‑quantitative PCR. T‑helper (Th)1 [CD4+; interferon (IFN)‑γ+] and Th2 [CD4+; interleukin (IL)‑4+] expression in peripheral blood mononuclear cells was evaluated using flow cytometry. Following the establishment of a 2,4‑dinitrofluorobenzene‑induced C57BL/6 mouse AD model, Th1 (CD4+IFN‑γ+) and Th2 (CD4+IL‑4+) expression was analyzed in murine spleen cells via flow cytometry. Plasmids were transfected into 293T cells and at 48 h post‑transfection, cells were analyzed using a luciferase assay system. The results revealed that the AD group had a significantly lower Th1/Th2 ratio and a significantly higher miR‑146a expression compared with the control group (P<0.05). Furthermore, a decreased Th1/Th2 ratio and a significantly increased miR‑146a expression were observed in the model group compared with the control group (P<0.01). We also conducted a dual‑luciferase assay to determine whether small ubiquitin‑related modifier 1 (SUMO1) if the target gene of miR‑146a. We observed a ~30% decrease in the relative luciferase activity in cells containing the 3'‑untranslated region of SUMO1 + miR‑146a). The results of the luciferase assay indicated that may be a direct mRNA target of miR‑146a; however, the quantification of band density of SUMO1 expression following western blotting did not significantly differ. The development of animal models in AD research is of vital importance. The results revealed that miR‑146a may be a potential regulator involved in the pathogenesis of AD. Furthermore, the current study determined that miR‑146a could be a valuable marker of AD and thus, may be applied in the development of therapeutic strategies for treating AD.

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Role of macrophages in the pathogenesis of atopic dermatitis.

Publications

Role of macrophages in the pathogenesis of atopic dermatitis.

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