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British Journal of Dermatology 04/2011; 165(2):437-9. · 3.67 Impact Factor
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ABSTRACT: Acute generalized exanthematous pustulosis (AGEP) is a diffuse pustular disorder that usually begins in intertriginous folds with widespread erythema. The causes in the majority of the cases are drugs. T cells and interleukin (IL)-8 play roles in the development of AGEP, but the mechanism remains to be elucidated. We investigated the involvement of Th17 cells and their cytokine IL-22 in the pathogenesis.
Three patients with AGEP were enrolled in this study. The percentages of IL-17(+) Th17 cells, interferon γ(+) T cells and IL-4(+) T cells were measured in the patients' peripheral blood lymphocytes by intracellular cytokine staining and flow cytometry. The concentration of IL-22 in the sera was measured by enzyme-linked immunosorbent assay.
The percentages of Th17 cells were markedly higher in all three patients than healthy control individuals. The frequencies of interferon γ(+) T cells were slightly high in the patients compared with the control, and there was no definite tendency in IL-4(+) T-cell frequencies. The concentration of IL-22 was remarkably high in all patients when compared with normal subjects with levels under detection.
Th17 cells and their produced cytokine IL-22 were elevated in the peripheral blood of patients with AGEP. As IL-17 and IL-22 cooperatively stimulate keratinocytes to produce IL-8, IL-8 may contribute to the accumulation of neutrophils in the lesional epidermis of AGEP.
Journal of the European Academy of Dermatology and Venereology 04/2011; 25(4):485-8. · 2.98 Impact Factor
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Clinical and Experimental Dermatology 03/2011; 36(5):555-7. · 1.20 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 02/2011; 25(2):242-4. · 2.98 Impact Factor
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Clinical and Experimental Dermatology 12/2010; 36(3):315-7. · 1.20 Impact Factor
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British Journal of Dermatology 09/2010; 164(1):204-5. · 3.67 Impact Factor
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British Journal of Dermatology 05/2010; 162(5):1152-4. · 3.67 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 04/2010; 24(11):1365-6. · 2.98 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 09/2009; 24(3):358-9. · 2.98 Impact Factor
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British Journal of Dermatology 09/2009; 161(4):968-70. · 3.67 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 09/2009; 24(4):495-6. · 2.98 Impact Factor
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T Mori,
K Ishida,
S Mukumoto,
Y Yamada,
G Imokawa,
K Kabashima,
M Kobayashi,
T Bito, M Nakamura,
K Ogasawara,
Y Tokura
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ABSTRACT: Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.
British Journal of Dermatology 08/2009; 162(1):83-90. · 3.67 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 06/2009; 23(11):1333-5. · 2.98 Impact Factor
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ABSTRACT: Bepotastine besilate is an antihistaminic drug of the second generation with superior clinical responses. In this study, we investigated whether bepotastine modulates the production of cytokines/chemokines and the expression of CD54 in human epidermal keratinocytes. The production of IL-1alpha, CXCL10, and CCL17 and the expression of CD54 were significantly suppressed by the addition of bepotastine. Bepotastine exerts its antiallergic action on keratinocytes by suppressing the production of certain proinflammatory cytokines, both Th1 and Th2 chemokines, and possibly by inhibiting the expression of CD54.
Skin pharmacology and physiology 01/2009; 22(1):45-8. · 2.92 Impact Factor
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ABSTRACT: Epidermal keratinocytes are involved in the skin innate immunity and express toll-like receptors (TLRs) and other innate immune proteins. The epidermis is continuously exposed to pathogenic gram-positive bacteria or fungi. However, few studies have examined the function and expression of innate immune proteins in keratinocytes. Histamine, which is well known for itch and allergy, is closely associated with innate immunity, but its influence on epidermal innate immunity is still unclear.
To clarify the expression of innate immune proteins in keratinocytes stimulated by ligand pathogen-associated molecules, and the function of histamine in this process.
We investigated the effects of lipopeptide (MALP-2, 1-100 ng mL(-1); ligand for TLR2), peptidoglycan (PGN, 0.02-2 microg mL(-1); ligand for NOD2) and beta-glucan (1-100 microg mL(-1); ligand for dectin-1) in the presence or absence of histamine on mRNA expression of TLR2, NOD2 and dectin-1 as well as human beta-defensin 2 by quantitative real-time polymerase chain reaction in cultured normal human epidermal keratinocytes. TLR2 expression was also examined at the cell surface and intracellularly, as determined by flow cytometry and confocal microscopy. The quantities of interleukin (IL)-1alpha and IL-8 produced by keratinocytes were measured using enzyme-linked immunosorbent assay.
At the mRNA level, TLR2 was enhanced by PGN but not by its ligand MALP-2 or by beta-glucan; NOD2 was easily induced by all three ligands; and dectin-1 was enhanced by its ligand beta-glucan. These enhanced expressions were further augmented by histamine at 1 microg mL(-1). While the surface expression of TLR2 was barely detectable by flow cytometry even after stimulation, the intracellular expression of TLR2 was apparently elevated by PGN and further promoted by histamine. A confocal microscopic analysis also revealed the enhanced expression of TLR2 in the cytoplasm. The expression of TLR2, NOD2 and dectin-1 was functional, as these pathogen-associated molecules induced the production of IL-1alpha, IL-8 and defensin, and again, histamine greatly enhanced this production.
Our study demonstrated that the expression of functional innate immune receptors is augmented by the pathogen-associated molecules in a ligand-feed forward or nonrelated manner in keratinocytes, and histamine promotes their expression and the resultant production of cytokines and defensins.
British Journal of Dermatology 11/2008; 160(2):297-304. · 3.67 Impact Factor
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Journal of the European Academy of Dermatology and Venereology 09/2008; 23(6):708-9. · 2.98 Impact Factor
