Hirotoshi Furukawa

Fukushima Medical University, Hukusima, Fukushima, Japan

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Publications (7)14.03 Total impact

  • Yasunobu Kato · Taeko Nakamura · Hirotoshi Furukawa · Koichiro Nakamura · Fumio Kaneko ·

    01/2006; 21(2):211-214. DOI:10.5227/skincancer.21.211
  • F. Kaneko · K. Nakamura · H. Furukawa · N. Oyama · T. Nakamura · X. Zheng ·
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    ABSTRACT: It is well known that two different photobiologic processes mainly take place when the human skin is exposed to ultraviolet (UV) light. The long waves of UVA and visible light (320–400 nm) irradiation causes skin tanning by melanocytic activation and the short waves of UVB (280–320 nm) can elicit variety of biologic action in cutaneous keratinocytes, melanocytes and other skin component cells. The sensitivity to the UV lights is generally depending on the three kinds of the skin type classified by the proposal of Pathak et al. [1]. The skin sensitivity of Japanese population, however, seems to be different from that of Caucasian's population because of the differences in genetic background and skin color, as indicated by Satoh and Kawada [2]. They tried to classify into three groups as J-I (always burn and rarely tan), J-II (moderately burn and moderately tan) and J-III (never burn and always tan) by the skin types to UV lights for the sun-tanning and sun-burning. Comparing these two criteria, a general concern indicates that J-I–III may correspond to the skin type II–IV of the Fitzpatrick's classification, respectively. Based on the Japanese skin types, the incidence of skin cancers and precancerous lesions related to the long-term exposure of sun-light was epidemiologically estimated by Araki et al. [3]. According to their results for several years (1992–1998), the overall number of skin cancers and precancerous states in Japanese was demonstrated to be small in comparison with the incidence of Caucasian's population, even though the people sets in areas of higher ambient solar radiation. However, working outdoors having J-I and/or a history of severe sunburn during childhood were found to be important risk factors, particularly among people of over 60 years of age. Regarding skin cancers and sun-exposed areas, we compared between 20 patients with skin cancers (males 13 and females seven) (average 65 years old) (Table I) and 24 controls (males 10 and females 14), who were selected as similar ages to the patients at random, in their skin types and life environments by a questionnaire system. The skin types of the patients were J-I (15%), J-II (40%), and J-III (35%) and those of controls were J-I (4.2%), J-II (62.5%), and J-III (4.2%), respectively. The patient group tended not to protect from sun exposure and most of them were farmers. UV exposure is known to induce modulation of the skin immune system which Langerhans cells decrease in number in the epidermis, and on the other hand it is supposed that interleukin IL-10 producing macrophages (CD11b+) expand in the dermis. Not only IL-10, but also tumor necrosis factor (TNF)-α from macrophages and mast cells in the dermis seem to increase and suppress Th1 immune responses of the epidermis and Th2 immune responses might be induced by UV irradiation [4]. Recently, it has been reported, however, that in patients with polymorphous light eruption (PLE), the expression of TNF-α, IL-4, and IL-10 is reduced by UVB irradiation and that PLE appearance is related to UVB-induced immunosuppression [5]. Then, we attempted to study UVB effects on atopic disease and chronic inflamed skin diseases in the therapeutic advantage, although it is harmful for the patients to be cutaneous carcinogenesis. The epidermal keratinocytes are capable of producing CC chemokines in the local Th2 response, as seen in atopic dermatitis, mycosis fungoides, etc. [6]. Thymus and activated-related chemokine (TARC) is one of the chemokines produced by keratinocytes which selectively activate lymphocytes of Th2 subset expressing CCR4 (receptor for TARC) [7]. Accumulating evidence has suggested that these chemokines have primary pathogenic importance in Th2 skin diseases. In order to find the effects of UVB irradiation on the production of TARC, we used a human keratinocyte HaCaT cell line. As assessed by RT-PCR and ELISA, UVB irradiation significantly decreased the expression of TARC mRNA and protein in HaCaT cells stimulated with interferon-γ (IFN-γ) and TNF-α in a dose-dependent manner. The down-regulation of TARC expression may be mediated in part by activation of the particular transcription, signal transducer and activator of transcription 1 (STAT 1), since it has shown that STAT 1 DNA-binding was down-regulated by UVB irradiation. Our results suggest that STAT 1 and other transcription factors play an important biological role in immune system of human skin irradiated by UVB and may support the results of Kolgen et al. [5]. In this point of view, UVB irradiation will be a therapeutic tool for skin diseases related to Th2 type reaction, such as atopic dermatitis, mycosis fungoides, etc., although we need to optimize adequately the use of UVB in patients with J-I skin type or those of whom have the episode of severe sun-burn after UVB irradiation. 1. Pathak, M.A., Nghiem, P. and Fitzpatrick, T.B. Acute and chronic effects on the skin. In: Fitzpatrick's Dermatology in General Medicine, 5th edn (Freedberg, I.M., Eisen, A.Z., Wolf, K., Austen, K.F., Goldsmith, L.A., Katz, S.I. and Fitzpatrick, T.B. eds), pp. 1598–1607. McGraw-Hill, New York (1999). 2. Satoh, Y. and Kawada, A. Action spectrum for melanin pigmentation to ultraviolet light, and Japanese skin typing. In: Brown Melanoderma: Biology and Diseases of Epidermal Pigmentation (Fitzpatrick, T.B., Wick, M.M. and Toda, K. eds), pp. 87–95. University of Tokyo Press, Tokyo (1986). 3. Araki, K., Nagano, T., Ueda, M., Washio, F., Watanabe, S., Yamaguchi, N. and Ichihashi, M. Incidence of skin cancers and precancerous lesions in Japanese- Risk factors and prevention. J. Epidemiol. 9, S14–S21 (1999). 4. Teunissen, M. B., Piskin, G., Nuzzo, S. et al. Ultraviolet B radiation induces a transient appearance of IL-4+ neutrophils, which support the development of Th2 responses. J Immunol. 168, 3732–3739 (2002). 5. Kolgen, W., van Meurs, M., Jongsma, M. et al. Differential expression of cytokines in UVB-exposed skin of patients with polymorphous light eruption. Arch. Dermatol. 140, 295–302 (2004). 6. Kakinuma, T., Sugaya, M., Nakamura, K., Kaneko, F., Wakugawa, M., Matsushima, K. and Tamaki, K. Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J. Am. Acad. Dermatol. 48, 23–30 (2003). 7. Imai, T., Nagira, M., Tkagi, S. et al. Selective recruitment of CCR4-binding Th2 cells toward antigen-presenting cells by the CC chemokins thymus and activation-regulated chemokine and macrophage-derived chemokine. Int. Immunol. 11, 81–88 (1999).
    International journal of cosmetic science 02/2005; 27(1). DOI:10.1111/j.1467-2494.2004.00254_14.x · 1.38 Impact Factor
  • Hirotoshi Furukawa · Masanobu Takahashi · Koichiro Nakamura · Fumio Kaneko ·
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    ABSTRACT: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.
    Journal of Dermatological Science 12/2004; 36(3):165-72. DOI:10.1016/j.jdermsci.2004.09.001 · 3.42 Impact Factor
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    ABSTRACT: Thymus and activation regulated chemokine (TARC) is a CC chemokine that attracts CCR4+ T cells. We reported previously that TARC is an important chemokine that defines Th2 imbalance in the pathogenesis of atopic dermatitis (AD). This study was undertaken to clarify TARC producing cells in peripheral blood mononuclear cells (PBMCs), the regulation of dust mite-allergen clude extract (DME) and different immunosuppressive drugs (Tacrolimus (FK506), cyclosporine (CsA), dexamethasone (Dex)) on TARC production by peripheral PBMCs from AD patients in vitro. Monocyte derived dendritic cells (MoDCs) were generated from and TARC mRNA levels were examined and comapared with those from T cells in PBMCs from AD patients. PBMCs were cultured with or without DME and/or immunosuppressive drugs (Tacrolimus, CsA, Dex) for 7 days and TARC levels were measured. PBMCs from AD patients which were cultured with DME stimulation for 7 days showed significantly higher levels of TARC production than those from healthy controls. RT-PCR demonstrated that TARC mRNA was expressed in CD4+ T cells, CD8+ T cells and MoDCs. Tacrolimus, CsA and Dex individually suppressed TARC production by PBMCs from AD patients which were co-cultured with DME for 7 days. Gel shift analysis revealed differential inhibitory effects of these immunosuppressive drugs on NFkappaB activity in PBMCs from AD patients. Our data demonstrate that TARC producing cells are MoDCs, T cells as well as epidermal keratinocytes in AD. We suggest that MoDCs might regulate the immune responses by attracting T cells and CD25+ T cells in the pathogenesis of AD. We also showed the important role of DME on TARC production and the inhibitory effect of the immunosuppressive drugs on TARC production by PBMCs from AD patients, that can regulate ongoing immune responses in the pathogenesis of AD.
    Journal of Dermatological Science 07/2004; 35(1):35-42. DOI:10.1016/j.jdermsci.2004.02.008 · 3.42 Impact Factor
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    ABSTRACT: Anti-p200 pemphigoid with autoantibodies against the 200-kD dermal antigen has recently been identified. Our patient showed small and tense blisters on her face and trunk. Immunoblotting (IB), using extracts of normal human epidermis and dermal skin, and immunoelectron microscopy (IEM), using normal human skin, were performed using the patient's serum. IB analysis showed that the patient's serum did not react with 180-kD bullous pemphigoid (BP180) or BP230 antigens; however, IgG autoantibodies in the patient's serum reacted with a 200-kD dermal antigen as well as the 290-kD epidermolysis bullosa acquisita (EBA) antigen. IEM showed that IgG antibodies in the patient's serum bound to the lamina lucida, as well as both the lamina densa and sublamina densa. After the treatment with prednisolone, the 290-kD protein reactivity decreased rapidly; however, the 200-kD protein band was still observed. We describe a rare case with immunoreactive autoantibodies against both a novel dermal 200-kD autoantigen and the 290-kD EBA antigen.
    Dermatology 02/2004; 209(2):145-8. DOI:10.1159/000079601 · 1.57 Impact Factor
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    ABSTRACT: Thymus- and activation-regulated chemokine (TARC/CCL17) and its receptor, CC chemokine receptor 4 (CCR4), have been proven to be involved in a number of allergic diseases, especially atopic dermatitis (AD). The purpose of this study was to examine the expression and distribution of TARC and CCR4 mRNAs in samples of AD (n=15, acute lesions 8, chronic lesions 7) and normal skin (n=6). The expression and distribution of TARC and CCR4 mRNAs were detected with the in situ reverse transcription (RT) -polymerase chain reaction (PCR) technique. TARC mRNA was expressed in epidermal keratinocytes, dermal endothelial cells and infiltrating cells. CCR4 mRNA was expressed in dermal endothelial cells and infiltrating cells. In acute AD lesional skin, there were more positive cells, and the staining intensity was stronger than in chronic lesions (p<0.05). The distribution of positive cells was as follows: In the epidermis, keratinocytes in the basal layer showed the strongest staining, and keratinocytes in the spinous layer showed moderate staining; the superficial area showed faint staining. In the dermis, infiltrating cells located in the superficial area of the dermis showed the strongest staining, positive staining intensity became weaker and the percentage of positive cells became less as the location became deeper. There were no positive cells in normal skin. These data further substantiate the role of TARC/CCR4 in the pathogenesis of AD.
    The Journal of Dermatology 02/2003; 30(1):26-32. · 2.25 Impact Factor
  • Michiko Tojo · Keiji Iwatsuki · Hirotoshi Furukawa · Masabumi Takahashi · Fumio Kaneko ·
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    ABSTRACT: Neutrophilic eccrine hidradenitis (NEH) is a rare, transient complication, which usually occurs in patients with leukemia receiving various chemotherapeutic regimens. However, similar eruptions have been observed in other conditions, including HIV-positive patients, and are often preceded by the onset of malignancies. We report the first case of NEH arising in a patient with actinic reticuloid syndrome who had been treated with methotrexate.
    European journal of dermatology: EJD 01/2002; 12(2):198-200. · 1.99 Impact Factor