Oral Administration of Chymase Inhibitor Improves Dermatitis in NC/Nga Mice

Watanabe, Naohiro; Tomimori, Yoshiaki; Terakawa, Maki; Ishiwata, Kenji; Wada, Adumi; Muto, Tsuyoshi; Tanaka, Taisaku; Maruoka, Hiroshi; Nagahira, Kazuhiro; Nakatsuka, Takashi; Fukuda, Yoshiaki

doi:10.1038/sj.jid.5700708

Cited by 17 publications

(11 citation statements)

References 12 publications

(5 reference statements)

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“…Hence, this represents an ideal candidate gene for the intrinsic form of this disease [145]. The use of small-molecule chymase-specific inhibitors in animal models of AD demonstrated the anti-inflammatory efficacy of these substances, with relevant reduction of mast cell and eosinophil infiltration into the lesions [146]. These observations suggest that chymase inhibition may potentially represent a novel therapeutic approach to AD [147].…”

Section: Evidence Of Epidermal Barrier Dysfunction In Admentioning

confidence: 97%

Pathobiology of Chronic Inflammatory Skin Diseases: Interplay Between Keratinocytes and Immune Cells as a Target for Anti-Inflammatory Drugs

Albanesi

Pastore

2010

CDM

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Inflammatory dermatoses encompass an enormous area of dermatopathology. These diseases are triggered and maintained by aberrant responses of the cells of the skin immune system. In the last decade it has become clear that epidermal keratinocytes are highly active immunological cells, with a major control over the acute and the chronic phase of skin inflammation by means of cytokine/chemokine production and surface molecule expression. In their turn, these rather disease-specific events driven by keratinocytes lead to a rich inflammatory infiltrate in the whole skin including the upper layers of the epidermis, and eventually in the aggravation and/or perpetuation of the skin disorder. Recently introduced single molecule-targeted biological drugs are offering the best demonstration that a fine definition of the molecular pathways underlying skin disorders is now necessary to identify the relevant therapeutic targets and finally obtain successful treatment of these diseases. In this review, we will summarize recent progress in our understanding of the immunologic basis of psoriasis, allergic contact dermatitis and atopic dermatitis, with special emphasis on potentially effective targets for novel anti-inflammatory drugs.

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Section: Evidence Of Epidermal Barrier Dysfunction In Admentioning

confidence: 97%

Pathobiology of Chronic Inflammatory Skin Diseases: Interplay Between Keratinocytes and Immune Cells as a Target for Anti-Inflammatory Drugs

Albanesi

Pastore

2010

CDM

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“…Additionally, chymase has stimulated cutaneous angiogenesis and contributed to cell damage in AD by increasing the expression of metalloproteinases (10). In mouse models, a chymase inhibitor has been shown to ameliorate the symptoms of AD (11).…”

mentioning

confidence: 99%

Decrease in Chymase Activity is Associated with Increase in IL-6 Expression in Mast Cells in Atopic Dermatitis

Ilves¹,

Harvima²

2015

Acta Derm Venerol

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Mast cell chymase and interleukin (IL)-6 can be involved in atopic dermatitis and chymase can degrade IL-6. Our aim was therefore to study the expression of mast cell chymase and IL-6 in atopic skin using enzyme- and immunohistochemistry and to analyse their interaction in vitro. Chymase activity was significantly reduced in mast cells in skin lesions whereas the percentage of IL-6(+) mast cells was increased. Low recombinant human (rh)-chymase concentration (10-100 ng/ml) stimulated and higher concentration (1,000 ng/ml) inhibited the proliferation of T cells and peripheral blood mononuclear cells. Rh-IL-6 inhibited T-cell proliferation, and even inhibited the proliferation induced by rh-chymase. Pretreatment of rh-IL-6 with a high rh-chymase concentration prevented the IL-6-induced inhibition in T-cell proliferation. The results suggest that reduction in chymase activity can give rise to increased cellular effects of mast cell IL-6 and that chymase and IL-6 can modify each other's effects.

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“…Chymase inhibitors including SUN13834 (or SUN13350, the free form of SUN13834) and SUN C8257 have been shown to improve dermatitis in several animal models of atopic dermatitis [3,8,9]. The mechanisms of such chymase inhibitors for ameliorating dermatitis likely include inhibition of inflammatory cell recruitment and activation of stem cell factor [8].…”

Section: Introductionmentioning

confidence: 98%

Pharmacokinetic/pharmacodynamic analyses of chymase inhibitor SUN13834 in NC/Nga mice and prediction of effective dosage for atopic dermatitis patients

Ogata¹,

Fujieda²,

Terakawa³

et al. 2011

International Immunopharmacology

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Oral Administration of Chymase Inhibitor Improves Dermatitis in NC/Nga Mice

Cited by 17 publications

References 12 publications

Pathobiology of Chronic Inflammatory Skin Diseases: Interplay Between Keratinocytes and Immune Cells as a Target for Anti-Inflammatory Drugs

Pathobiology of Chronic Inflammatory Skin Diseases: Interplay Between Keratinocytes and Immune Cells as a Target for Anti-Inflammatory Drugs

Decrease in Chymase Activity is Associated with Increase in IL-6 Expression in Mast Cells in Atopic Dermatitis

Pharmacokinetic/pharmacodynamic analyses of chymase inhibitor SUN13834 in NC/Nga mice and prediction of effective dosage for atopic dermatitis patients

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