Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis–like lesions

Vestergaard, Christian; Yoneyama, Hiroyuki; Murai, Motohiko; Nakamura, Kimie; Tamaki, Kunihiko; Terashima, Yuya; Imai, Toshio; Yoshie, Osamu; Irimura, Tatsuro; Mizutani, Hitoshi; Matsushima, Kouji

doi:10.1172/jci7613

Cited by 386 publications

(334 citation statements)

References 41 publications

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“…It has been reported that IL-10 protein was localized in large oval cells resembling monocytes in the dermal perivascular infiltrate of atopic lesions, 8,28 and the number of dermal macrophages in atopic lesions of NC/Nga mice increased when compared with nonlesional skin. 9 Leung et al 29 reported that macrophages were the predominant inflammatory cells in chronic AD lesions. Furthermore, it was recently demonstrated that engagement of FceRI, a high-affinity receptor for IgE, with IgE and anti-IgE antibodies, induces the production of IL-10 in human monocytes.…”

Section: Antisense Oligonucleotides For Il-10 Alleviate Dermatitis T mentioning

confidence: 99%

“…31,32 In addition, Nakamura et al 33 reported that a single topical delivery of NF-kB decoy ODNs significantly regressed atopic dermatitis in NC/Nga mice. TARC is the primary chemokine in ADlike lesions of NC/Nga mice, 9 and TARC serum levels are closely related to disease activity in human AD. 34 Furthermore, TARC production was regulated by both IL-10 and NF-kB, the former enhances IFN-g-and TNF-ainduced TARC production 10 and the latter is a crucial transcription factor in TARC expression.…”

Section: Antisense Oligonucleotides For Il-10 Alleviate Dermatitis T mentioning

confidence: 99%

“…7 Of these cytokines/chemokines, IL-10 is overexpressed by monocytes/macrophages and the Th2 lymphocytes in the skin lesions of AD patients. 8 In addition, IL-10 augments the production of thymus and activation regulated chemokine (TARC), which is a Th2-specific chemokine and is known for overexpression in AD lesions 9 and in human keratinocytes treated by TNF-a and IFN-g. 10 Furthermore, as IL-10 inhibits the apoptosis of T cells activated by ligation of T-cell receptors and IL-2 treatment, 11 IL-10 may be involved in the dysregulated apoptosis of T cells in the skin lesions of AD. This dysregulated apoptosis is considered to be an important factor in the pathogenesis of AD.…”

Section: Introductionmentioning

confidence: 99%

“…Immunohistochemical examination of the lesions in conventional NC/Nga mice reveal hyperkeratosis, acanthosis, and parakeratosis, all of which resemble the typical features of the skin observed in patients with AD. 9,15 The lesions show lymphocyte infiltration with a high CD4/CD8 ratio, macrophage infiltration, and mast cell and eosinophil degranulation. In addition, the level of IgE in the blood gradually increases to high levels.…”

Section: Introductionmentioning

confidence: 99%

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Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

et al. 2004

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IL-10 is overexpressed in skin lesions of atopic dermatitis (AD) patients and believed to be an important factor in the pathogenesis of the disease. Thus the regulation of IL-10 production is a potential solution for immunotherapeutic intervention in AD. We examined the topical delivery of an antisense oligonucleotide for mouse IL-10 (AS6) and the therapeutic effect on the skin lesions of NC/Nga mice, a human AD model. Using an iontophoresis system, about 30% of the applied dose of AS6 penetrated the skin and was distributed in the epidermis and upper dermis. Topically delivered AS6 decreased the levels of mRNA and protein of IL-10 in the lesions of NC/Nga mice, with no effect on IL-4 levels. The dorsal lesions of NC/Nga mice disappeared with repeated topical application of AS6. Topically delivered AS6 showed an inhibitory effect on the production of IL-10 in the skin lesions of NC/Nga mice and had a therapeutic effect on the established dermatitis.

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Section: Antisense Oligonucleotides For Il-10 Alleviate Dermatitis T mentioning

confidence: 99%

Section: Antisense Oligonucleotides For Il-10 Alleviate Dermatitis T mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

et al. 2004

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“…MDC is a potent chemoattractant for dendritic cells (DC), natural killer (NK) cells and Th2 subset of T cells 1,2 and is involved in chronic inflammation or homing of DC and lymphocytes. 3,4 Recent studies have demonstrated a pivotal role of MDC in the protection of mice from cecal ligation and puncture-induced lethality. 5 It was reported that T cells attracted by MDC gene-transfected cell lines could predominantly produce Th2-type cytokines, such as IL-4.…”

Section: Introductionmentioning

confidence: 99%

Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity

et al. 2002

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Dendritic cells as a major source of macrophage-derived chemokine/CCL22in vitro andin vivo

et al. 2001

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Macrophage‐derived chemokine (MDC)/CCL22 is a CC chemokine active on dendritic cells (DC), NK cells and Th2 lymphocytes. The present study was aimed at comprehensively investigating MDC production in vitro and in vivo. DC were the most potent producers of MDC among leukocytes tested. Endothelial cells did not produce MDC under a variety of conditions. Signals that induce maturation (lipopolysaccharide, IL‐1, TNF, CD40 ligand, recognition of bacteria and yeast) dramatically augmented MDC production, and dexamethasone and vitamin D3 blocked it. Prostaglandin E2, which blocked the acquisition of IL‐12 production and the capacity to promote Th1 generation, did not affect MDC production. Using mass spectrometry‐based techniques, DC supernatants were found to contain N‐terminally truncated forms of MDC [MDC(3–69), MDC(5–69) and MD(C7–69)] as well as the full‐length molecule. In vivo, CD1a+, CD83+, MDC+ DC were found in reactive lymph nodes, and in Langerhans' cell histiocytosis. Skin lesions of atopic dermatitis patients showed that CD1a+ or CD1b+ DC, and DC with a CD83+ phenotype were responsible for MDC production in this Th2‐oriented disorder. Thus, DC are the predominant source of MDC in vitro and in vivo under a variety of experimental and clinical conditions. Processing of MDC to MDC(3–69) and shorter forms which do not recognize CCR4 is likely to represent a feedback mechanism of negative regulation.

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Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis–like lesions

Cited by 386 publications

References 41 publications

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice

Macrophage-derived chemokine gene transfer results in tumor regression in murine lung carcinoma model through efficient induction of antitumor immunity

Dendritic cells as a major source of macrophage-derived chemokine/CCL22in vitro andin vivo

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