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Biomedical subjects

A Asahina

Publications and source records attributed to A Asahina.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin 12 production by monocytes from patients with psoriasis and its inhibition by ciclosporin A.

BACKGROUND: Psoriasis is a T-helper (Th)1 cytokine-mediated chronic skin disease and interleukin (IL)-12 has been shown to play a major role in the development of Th1 responses. OBJECTIVES: To elucidate the role of IL-12 in the pathogenesis of psoriasis and to study the effect of ciclosporin A (CsA) on Th1 deviation of this disease. PATIENTS/METHODS: We investigated IL-12 production by stimulated monocytes from patients with psoriasis who were treated with or without CsA. Monocytes were stimulated with interferon-gamma plus lipopolysaccharide (LPS) or Staphylococcus aureus Cowan strain I (SAC). The amount of IL-12 p70 produced by stimulated monocytes was evaluated by enzyme-linked immunosorbent assay. RESULTS: Compared with those from normal controls, LPS- but not SAC-stimulated monocytes from patients with psoriasis produced significantly higher amounts of IL-12. Interestingly, LPS-stimulated monocytes from patients with psoriasis treated with CsA produced significantly decreased amounts of IL-12 compared with those patients not treated with CsA. CONCLUSIONS: Our results suggest that IL-12 production by monocytes may have a critical role in the pathogenesis of psoriasis, and that the therapeutic effect of CsA on psoriasis may be achieved by correcting the deviation of the Th1/Th2 balance.

Adult↗
PubMed2005

Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells.

Eotaxin-2/CCL24 and eotaxin-3/CCL26 are CC chemokines and their receptor, CC chemokine receptor 3 is preferentially expressed on eosinophils. It was reported that vascular endothelial cells and dermal fibroblasts produced CCL26. However, the regulation of CCL24 and CCL26 production in keratinocytes has not been well documented. We investigated the expression and production of CCL24 and CCL26 in the human keratinocyte cell line, HaCaT cells. Reverse transcription and polymerase chain reaction was performed using these cells and Enzyme-linked immunosorbent assay was carried out using supernatant of these cells. The production of CCL24 in HaCaT cells was slightly enhanced by IL-4 and that of CCL26 was strongly enhanced by IL-4 and IL-13. Furthermore, TNF-alpha generated a synergistic effect on IL-4 enhanced CCL26 production. Dexamethasone, IFN-gamma and the p38 mitogen-activated protein kinase inhibitor SB202190 inhibited IL-4 enhanced CCL26 production. IL-4 enhanced production of CCL26 was inhibited by leflunomide and JAK inhibitor 1, but not by JAK3 inhibitor, which indicates that it is mediated by JAK1-STAT6-dependent pathway. This result also strongly suggests the involvement of the type 2 IL-4 receptor in IL-4 enhanced production of CCL26. These results suggest that keratinocytes are involved in the migration of CC chemokine receptor 3 positive cells such as eosinophils in a Th2-dominant situation like atopic dermatitis.

Cell Line, Tumor↗
PubMed2004

A case of primary cutaneous anaplastic large cell lymphoma with variant anaplastic lymphoma kinase translocation.

Anaplastic lymphoma kinase (ALK) is frequently observed in systemic anaplastic large cell lymphoma (ALCL), mostly in childhood or adolescence, but only rarely in primary cutaneous cases. We report a case of primary cutaneous ALCL (pcALCL) with cytoplasmic ALK expression. A 54-year-old woman with an ulcerative tumour on her forehead was admitted to our hospital. Histologically, there was an infiltrate consisting of atypical large lymphocytes and small lymphocytes in the dermis and fat tissue. Southern blot analysis showed monoclonal T-cell receptor Cbeta1 gene rearrangement. Atypical large lymphocytes were positive for CD30, CD4 and CD25, and negative for CD3 and CD79a. They were also positive for ALK only in the cytoplasm, and neurophosmin (NPM)-ALK fusion transcript was not detected by reverse transcription-polymerase chain reaction. This suggested that the translocation partner of the ALK gene in this case was different from NPM (variant translocation). The tumour on the forehead resolved in 1 month after biopsy. Nodular lesions recurred on the right knee, and were histologically identical with the forehead lesion. Our case suggests the existence of a subgroup with variant ALK translocation in pcALCL; examining NPM-ALK translocation in each case with ALK expression should be useful to characterize the disease further.

Anaplastic Lymphoma Kinase↗
PubMed2003

Dermatofibrosarcoma protuberans with COL1A1 (exon 18) -PDGFB (exon 2) fusion transcript.

BACKGROUND: Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been described in dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have been shown to be involved in the fusion with exon 2 of the PDGFB gene. Objectives We examined the breakpoint of the COL1A1 gene using the tumour specimen from the patient with DFSP. METHODS: Reverse transcriptase-polymerase chain reaction (PCR) was performed using cultured DFSP tumour cells. Nucleotide sequence analysis was carried out using the PCR product to identify the breakpoint. RESULTS: The COL1A1-PDGFB fusion transcript was detected from the tumour specimen. Sequence analysis revealed that exon 18 of the COL1A1 gene was fused with exon 2 of the PDGFB gene. CONCLUSIONS: This study identified a novel COL1A1 breakpoint, namely, exon 18 of the COL1A1 gene.

Adult↗
PubMed2003

Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, eotaxin-2/CCL24 and eotaxin-3/CCL26 were identified as CC chemokines that signal exclusively via the CCR3 receptor and have eosinophil-selective chemoattractant activity, as does eotaxin/CCL11. We previously reported that serum levels of thymus and activation-regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 were correlated with the severity of AD. In this report, we investigated the participation of eotaxin-2/CCL24 and eotaxin-3/CCL26 in AD, first measuring the serum levels of eotaxin-2/CCL24 and eotaxin-3/CCL26 in 30 patients with AD, 20 patients with psoriasis vulgaris and 20 healthy controls. The serum levels of eotaxin-3/CCL26 (but not eotaxin-2/CCL24) were significantly higher in patients with AD than in either healthy controls or patients with psoriasis vulgaris; furthermore, the eotaxin-3/CCL26 levels in patients with moderate and severe AD were significantly higher than eotaxin-3/CCL26 levels in patients with mild AD. The serum eotaxin-3/CCL26 levels tended to decrease after treatment, but there was no significant difference between groups. Moreover, the serum eotaxin-3/CCL26 levels were significantly correlated with the serum TARC/CCL17 and MDC/CCL22 levels, eosinophil numbers in peripheral blood and the scoring AD (SCORAD) index. Our study strongly suggests that serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, have a notable correlation with disease activity of AD and that eotaxin-3/CCL26, as well as TARC/CCL17 and MDC/CCL22, may be involved in the pathogenesis of AD.

Adult↗
PubMed2002

Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of T cells, eosinophils and macrophages in lesional skin. Recently, macrophage-derived chemokine (MDC)/CCL22, a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells, in addition to thymus and activation-regulated chemokine (TARC). We have previously reported that serum TARC levels correlate with the severity of AD. In this report, we investigated the participation of MDC in AD. First, we measured serum MDC levels in 45 patients with AD, 25 patients with psoriasis vulgaris and 25 healthy controls. Serum MDC levels in AD patients were significantly higher than those in healthy controls and psoriasis patients. Furthermore, the increases in serum MDC levels in AD patients were greater in the severely affected group than in the moderate or mild groups. We compared serum MDC levels in 11 AD patients, before and after treatment, and observed a significant decrease after treatment. Moreover, the serum MDC levels significantly correlated with the Scoring AD (SCORAD) index, serum soluble (s) E-selectin levels, serum soluble interleukin-2 receptor (sIL-2R) levels, serum TARC levels and eosinophil numbers in peripheral blood. Our study strongly suggests that serum MDC levels have a notable correlation with disease activity and that MDC, as well as the CC chemokine TARC, may be involved in the pathogenesis of AD.

Administration, Cutaneous↗
PubMed2001

Transforming growth factor-beta up-regulates CD40-engaged IL-12 production of mouse Langerhans cells.

Transforming growth factor (TGF)-beta is an immunosuppressive agent that is efficacious in suppressing a wide variety of cell-mediated immune responses. However, the direct effect of this cytokine on Langerhans cells (LC) has not been clarified. In this study, we examined its modulatory effects on the expression of co-stimulatory molecules and LC IL-12 production. A highly purified population of LC (>95%) was prepared from BALB/c mouse skin by the panning method using anti-I-Ad mAb. Semiquantitative reverse transcription-PCR analysis showed that LC express TGF-beta receptor II mRNA. Interestingly, TGF-beta1 enhanced IL-12 p40 production of anti-CD40/IFN-gamma-stimulated LC, despite its down-regulatory effect on CD40 expression. A bioassay using an IL-12-dependent T cell line demonstrated the correlation of the IL-12 p40 level with the bioactivity of IL-12. More importantly, it was found that in contrast to TGF-beta, granulocyte/macrophage colony-stimulating factor (GM-CSF) strikingly inhibits IL-12 production of anti-CD40/IFN--stimulated LC and that the level of LC IL-12 production is determined by the relative amounts of TGF-beta1 and GM-CSF. Taken together, these results suggest that the two cytokines produced in the skin microenvironment, namely TGF-beta and GM-CSF, exert their important effects on LC function by regulating the secretion of IL-12, a cytokine influencing the Th1-Th2 balance.

Animals↗
PubMed2001

Griseofulvin has a potential to modulate the expression of cell adhesion molecules on leukocytes and vascular endothelial cells.

Griseofulvin has been used as an antifungal drug for many years, but it has recently been shown effective for several inflammatory skin diseases. We therefore investigated its putative immunomodulatory roles by flow cytometric analysis of cell adhesion molecules on human leukocytes and human vascular endothelial cells. Griseofulvin downregulated L-selectin expression on neutrophils, but not on lymphocytes, in a dose-dependent manner. Griseofulvin did not affect CD11b/CD18 expression on neutrophils. On human dermal microvascular endothelial cells (HDMEC), griseofulvin inhibited the expression of TNF alpha-induced VCAM-1 dose-dependently, and this inhibition was fully reversible. Similarly, griseofulvin inhibited the induction of VCAM-1 expression on both TNF alpha- and IL-1 alpha-stimulated human umbilical vein endothelial cells (HUVEC). In addition, it partially inhibited the induction of E-selectin expression, whereas it had a marginal effect on ICAM-1 expression. Reverse transcription-polymerase chain reaction of TNF alpha-stimulated HDMEC showed inhibition of VCAM-1, but not ICAM-1 gene transcription. These results indicate potent immunomodulatory properties of griseofulvin, which may be associated with its feature as a microtubule antagonist.

Adjuvants, Immunologic↗
PubMed2001

Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules.

We have previously reported that griseofulvin inhibits VCAM-1 expression on human vascular endothelial cells. Since griseofulvin interferes with microtubule assembly, we used colchicine as another microtubule antagonist and compared it with griseofulvin to further characterize this inhibition. By flow cytometry, colchicine inhibited VCAM-1 induction on TNFalpha-stimulated human dermal microvascular endothelial cells (HDMEC) dose-dependently. Colchicine also inhibited VCAM-1 induction on both TNFalpha- and IL-1alpha-stimulated human umbilical vein endothelial cells (HUVEC). Although this inhibition was reversible, colchicine-treated cells showed slower restoration of its expression than griseofulvin-treated cells. Moreover, co-incubation with a microtubule stabilizer paclitaxel blocked this inhibition, and colchicine-treated cells were more resistant to this blocking than griseofulvin. RT-PCR of HDMEC showed inhibition of the transcript level of VCAM-1 by both antagonists. These results indicate intimate association between VCAM-1 expression and microtubules.

Cells, Cultured↗
PubMed2001

Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity.

BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by the predominant infiltration of TH2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) is a chemokine that attracts CC chemokine receptor 4-positive (CCR4+) or CCR8+ cells. OBJECTIVE: The purpose of this study was to investigate the participation of TARC in AD. METHODS: We measured serum TARC levels in 40 patients with AD, 20 healthy control subjects, and 20 patients with psoriasis. We also examined disease activity by using SCORAD score; serum soluble E-selectin, soluble IL-2 receptor, IgE, and GM-CSF levels; and eosinophil numbers in peripheral blood, as well as correlations between TARC levels and these factors. The positivity of CCR4 of CD4+CD45RO+ cells in PBMCs was examined by using FACS analysis. Immunohistochemical staining of TARC and GM-CSF was performed in the lesional skin of patients with AD. RESULTS: The serum TARC levels of patients with AD were significantly higher than those of healthy control subjects and patients with psoriasis. The serum TARC levels significantly correlated with eosinophil number (r = 0.61), SCORAD score (r = 0.60), and serum soluble E-selectin levels (r = 0.58) and weakly correlated with serum soluble IL-2 receptor levels (r = 0.34) in patients with AD. The TARC levels of patients with AD decreased after the treatment in accordance with the improvement of clinical symptoms. The CCR4 positivity of CD4+CD45RO+ cells in PBMCs of patients with AD was also higher than that of healthy control subjects. Immunohistochemical staining revealed that TARC was positive in keratinocytes in the epidermis and in vascular endothelial cells, T cells, and dendritic cells in the dermis. CONCLUSION: Serum TARC levels are associated with disease activity of AD, and TARC may play an important role in the pathogenesis of AD.

Administration, Oral↗
PubMed2001

Leukocytoclastic vasculitis with IgA deposits in angioimmunoblastic T cell lymphoma.

Angioimmunoblastic T cell lymphoma (AILD) is a type of peripheral T cell lymphoma associated with fever and generalized lymphadenopathy. Cutaneous manifestations are seen in approximately 40% of the patients. We report herein a Japanese male patient with AILD associated with generalized purpura. The histology of the purpura included leukocytoclastic vasculitis with IgA deposits, which is rare in this disease. Using in situ hybridization and PCR methods, we showed that the involved lymph node was positive for Epstein-Barr virus and that the purpura was negative.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Granulocyte/macrophage colony-stimulating factor inhibits IL-12 production of mouse Langerhans cells.

We investigated the capacity of mouse Langerhans cells (LC) to produce IL-12, a central cytokine in a Th1 type of immune responses. We prepared purified LC (>95%) from BALB/c mouse skin by the panning method using anti-I-Ad mAb. An ELISA showed that purified LC spontaneously produced IL-12 p40, and that its production was up-regulated following simultaneous stimulation with anti-CD40 mAb and IFN-gamma. Surprisingly, GM-CSF strikingly inhibited IL-12 p40 production by anti-CD40/IFN-gamma-stimulated LC (% inhibition = 97.0 +/- 0.9% at 1 ng/ml GM-CSF). Supernatants of 48-h cultured keratinocytes (KC) also caused the inhibition of LC IL-12 p40 secretion, and this effect was neutralized by anti-GM-CSF mAb. IL-1alpha (1 ng/ml)-stimulated KC produced much more GM-CSF than unstimulated KC (60.9 +/- 0.2 pg/ml vs 20.9 +/- 1.7 pg/ml), and IL-1alpha-stimulated KC supernatants strongly inhibited IL-12 p40 production by anti-CD40/IFN-gamma-stimulated LC (% inhibition = 89.4 +/- 1.4%). A bioassay using an IL-12-dependent T cell line demonstrated the correlation of the level of IL-12 p40 with the bioactivity of IL-12. These results provide important implications for the pathogenesis of atopic dermatitis, which involves the participation of LC and KC with the capacity to produce IL-12 and GM-CSF, respectively.

Animals↗
PubMed2000

Exacerbation of pustulosis palmaris et plantaris after topical application of metals accompanied by elevated levels of leukotriene B4 in pustules.

BACKGROUND: Pustulosis palmaris et plantaris (PPP) is a chronic inflammatory disease consisting of polymorphonuclear leukocyte infiltration, and is often exacerbated by focal infections such as tonsillitis. In some cases, metal allergy has been reported. OBJECTIVE: The purpose of this study was to evaluate (1) the significance of metal allergy in the formation of pustules, and (2) the participation of leukotriene (LT) B(4) in the formation of pustules of PPP. METHODS: Patch tests with metals were performed on 7 patients with PPP, and both pustular and plasma levels of LTB(4) were measured in these 7 patients before and 48 hours after metal patch tests. RESULTS: Palmoplantar pustules were exacerbated after the metal patch tests in all 7 patients. The mean levels of LTB(4) in plasma and pustules of the volar surface at 48 hours after the metal patch tests were significantly higher than those before the metal patch tests. CONCLUSION: Metals can be important in the pathogenesis of PPP by contributing to the induction of high LTB(4) concentration in the pustules.

Administration, Topical↗
PubMed1999

Functional CD40 ligand is expressed on epidermal Langerhans cells.

Epidermal Langerhans cells (LC) are bone-marrow-derived major histocompatibility complex (MHC) class II antigen-expressing antigen-presenting cells (APC) that comprise 1-3% of total epidermal cells (EC). LC express high levels of MHC class II antigen and augment costimulatory molecules such as B7-1, B7-2 during culture. In a previous report, using purified murine LC, we showed that freshly prepared LC (fLC) do not express CD40, whereas cLC express CD40. Tumor necrosis factor alpha (TNF-alpha) enhanced CD40 expression on LC during culture. We examined the expression of CD40L on LC and found that both fLC and cLC expressed mRNA for CD40L. FACS analysis revealed that cLC cultured for 36 h expressed CD40L but fLC did not. When we examined the cytoplasmic CD40L, however, both fLC and cLC expressed cytoplasmic CD40L. TNF-alpha, which up-regulated CD40 expression on LC during culture, did not modulate CD40L. Co-culture of purified LC ith anti-CD40L markedly inhibited the up-regulation of B7-1 expression on LC and caused partial inhibition of B7-2 expression during culture. These results indicate that CD40L is expressed on cLC, and that CD40L on LC modulates the expression of costimulatory molecules such as B7-1 and B7-2 on LC.

Animals↗
PubMed1999

Polymorphisms of HLA-DM genes in Japanese patients with psoriasis vulgaris.

We analysed the polymorphisms of HLA-DM genes in 85 unrelated Japanese patients with psoriasis vulgaris and 52 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of DMA*0101 was decreased (79% vs. 89%, P < 0.05) and that of DMA*0102 was increased (20% vs. 11%, P < 0.05) in the patients. However, neither of these remained significant after P-values were corrected for the number of comparisons made (Pc > 0.05). As we reported previously, HLA-C molecules are assumed to play a more important part than HLA-DM genes in the development of psoriasis vulgaris.

Adult↗
PubMed1999

Differential effects of cytokines and immunosuppressive drugs on CD40, B7-1, and B7-2 expression on purified epidermal Langerhans cells1.

Langerhans cells are MHC class II antigen-positive antigen-presenting cells in the epidermis. Recent studies have revealed that Langerhans cells express costimulatory molecules like B7-1 and B7-2 and the accessory molecule CD40. Although these molecules are important for the antigen-presenting function of Langerhans cells, little is known about the precise regulation of their expression on purified Langerhans cells. Using a panning technique, we purified epidermal Langerhans cells to around 95% purity. Freshly prepared Langerhans cells (fLC) expressed the mRNA for receptors for M-CSF (cfms), GM-CSF (GM-CSFR), and TNF-alpha (TNFRII). TNF-alpha markedly upregulated CD40 and B7-1 expression on Langerhans cells, but not B7-2 expression. GM-CSF moderately upregulated B7-1 and B7-2 expression, and slightly upregulated CD40 expression. M-CSF moderately upregulated B7-1 expression, but did not modulate CD40 or B7-2 expression. Dexamethasone (DEX) markedly inhibited CD40, B7-1, and B7-2 expression on Langerhans cells. Cyclosporin A (CsA) and FK506 slightly inhibited CD40 and B7-1 expression on Langerhans cells, but not B7-2. Furthermore, TNF-alpha restored the DEX-induced inhibition of CD40 expression on Langerhans cells, but not the inhibition of B7-1 or B7-2 expression. GM-CSF restored DEX-induced inhibition of CD40, B7-1, and B7-2 expression. M-CSF did not affect the DEX-induced inhibition of these molecule expressions. These data provide a better understanding of the role of selective cytokines and immunosupressive drugs in the modulation of the antigen-presenting capacity of Langerhans cells.

Animals↗
PubMed1998

Analysis of HLA class II and TAP alleles in Japanese patients with psoriasis vulgaris.

We investigated HLA class II and transporter associated with antigen processing (TAP) alleles in eighty-five unrelated Japanese patients with psoriasis vulgaris and fifty-two healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. The frequencies of DRB1*1502 and DQB1*0601 were increased in the patient group (DRB1*1502; 21% vs 12%, p < 0.05, DQB1*0601; 35% vs. 21%, p < 0.05), while the frequencies of DRB1*0406 and TAP2*E were decreased in the patients (DRB1*0406; 2% vs 9%, p < 0.05, TAP2*E; 4% vs 11%, p < 0.05). However, none of these remained significant after p values were corrected for the number of comparisons made (pc > 0.05). We also analysed specific amino acids on HLA class II molecules, but no significant difference was found between the two groups. Our previous reports clarified that aspartate at residue 9 (48% vs 20%, p < 0.002) and alanine at residue 73 (81% vs 48%, p < 0.0001) on HLA-C molecules were strongly associated with Japanese patients with PsV. These specific amino acids on HLA-C molecules are supposed to play more important roles compared with HLA class II and TAP alleles in the development of psoriasis vulgaris.

ATP Binding Cassette Transporter, Subfamily B, Mem↗