| Project/Area Number |
16590127
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Meiji Pharmaceutical University |
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Principal Investigator |
SUGITA Takashi Meiji Pharmaceutical University, Department of Microbiology, Associated Professor, 薬学部, 准教授 (10312076)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Atopic dermatitis / Malassezia / Steroid / Tacrolimus / Anti-fungal agent / 増悪因子 / リパーゼ / 菌相解析 / 遺伝子型 / アゾール |
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| Research Abstract |
1. Lipophilic Malassezia species colonized on skin surface in atopic dermatitis (AD) patients and healthy subjects was analayzed by culture-independent method. The patient with AD was controlled under the specific genotypic strain of Malassezia globosa and M. restricta.
2. Real-time PCR assay was established. Seven to 12 times more Malassezia colonized the head and neck compared to the trunk or limbs, and the species M. globosa and M. restricta accounted for approximately 80% of all Malassezia colonization at any body site.
3. We examined 125 strains of the eleven currently accepted Malassezia species using the agar dilution method. All strains of the eleven Malassezia species were very susceptible to both azole agents with minimum inhibitory concentrations (MIC) ranging from 0.016 to 0.25 μg/mL. Tacrolimus had antifungal activities against half of the strains, with MICs ranging from 16 to 32 ug/mL. A combination of azole agents and tacrolimus had a synergistic effect against Malassezia
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isolates based on a fractional inhibitory index (FIX) of 0.245 to 0.378. Our results suggest that a combination of ITC or KTZ with tacrolimus might be an effective therapy for reducing the number of Malassezia cells colonizing the skin surface in patients with AD.
4. Several Malassezia atopic allergens have been identified. Of these, Mala f6 (a cyclophilin homolog) is considered major atopic allergen because high levels of IgE antibodies against it is detected in the serum of patients with AD. This study investigated the influence of the calcineurin inhibitor tacrolimus on the expression of Malassezia atopic allergen genes. In the presence of tacrolimus, the expression of the Mala f6 gene of Malassezia was suppressed compared with the control expression, whereas their expression was not changed in the presence of the steroid (betamethasone valerate). This suggests that tacrolimus may contribute to the improvement of eczematous lesions via the suppression of Malassezia atopic allergen gene expression, in addition to its well-characterized anti-inflammatory effect. Less
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