PubMed Health⌕ Search

Biomedical subjects

Harumi Suzaki

Publications and source records attributed to Harumi Suzaki.

At least 19 recordsLinked to original sources
PubMed2006

Epinastine hydrochloride antagonism against interleukin-4-mediated T cell cytokine imbalance in vitro.

BACKGROUND: Interleukin (IL)-4 is well accepted to be a cytokine that plays many roles in the regulation of immune responses. Although the primary pharmacological target of antihistamines has been regarded as the histamine H1 receptor, there is little information about the influence of antihistamines on IL-4-mediated immune responses. The present study was undertaken to examine whether H1 receptor antagonists could modulate IL-4-mediated immune responses in vitro. METHODS: CD4+ T cells from normal human peripheral blood (1 x 10(6) cells/ml) were incubated with various concentrations of epinastine hydrochloride (EP) or chlorpheniramine (CH) for 30 min and then stimulated with 10.0 ng/ml IL-4. After 24 h, culture supernatants were collected and assayed for IL-5, IL-6, IL-13 and interferon-gamma by ELISA. The influence of EP on transcription factor activation and mRNA expression for cytokines was also examined. RESULTS: Addition of EP into cell cultures at more than 20.0 ng/ml significantly suppressed the production of IL-5, IL-6 and IL-13, which were increased by IL-4 stimulation. EP at more than 20.0 ng/ml also suppresses nuclear factor-kappaB activation, signal transducers and activators of transcription 6 phosphorylation and mRNA expression, which were upregulated by IL-4 stimulation. However, the ability of CD4+ T cells to produce interferon-gamma was decreased by IL-4 stimulation, which was dramatically restored by treatment with EP at more than 15.0 ng/ml. On the other hand, CH, a first-generation H1 receptor antagonist, could not inhibit cytokine production from CD4+ T cells in response to IL-4 stimulation, even when 90.0 ng/ml of the agent was added to cell cultures. CONCLUSION: The present results strongly suggest that EP, a second-generation H1 receptor antagonist, interferes with IL-4-activated signaling in CD4+ T cells and results in favorable modification of the allergic disease state or conditions.

Adult↗
PubMed2006

Effect of tranilast on matrix metalloproteinase production from neutrophils in-vitro.

Tranilast is an anti-allergic agent that blocks the release of chemical mediators, such as histamine and leukotrienes from mast cells, and has been reported to suppress keloid and hypertrophic scar formation. Since matrix metalloproteinases (MMPs) play an essential role in tissue remodelling, this study was undertaken to determine whether tranilast suppresses MMP production from neutrophils after lipopolysaccharide (LPS) stimulation in-vitro. Neutrophils from five healthy donors (1 x 10(5) cells/mL) were stimulated with 1.0 microg mL(-1) LPS in the presence or absence of various concentrations of tranilast for 24 h. MMP-7, MMP-8, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels in the culture supernatants were assayed by ELISA. In addition, the influence of tranilast on MMP mRNA expression and transcriptional factor activation in cells cultured for 12 h and 4 h was also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Tranilast inhibited MMP and TIMP-1 production from neutrophils when cells were treated with the agent at more than 5.0 x 10(-5) M. It also suppressed MMP mRNA expression and transcriptional factor activation induced in neutrophils by LPS stimulation. The results suggest that tranilast inhibits the formation of keloid scarring through the suppression of factors such as MMPs and TIMP, which are essential for tissue remodelling, from inflammatory cells.

Adult↗
PubMed2006

[Odor stick identification test for Japanese patients with olfactory disturbances].

In recent years, a new stick-type odor identification test, the odor-stick identification test for Japanese (OSIT-J) has been developed in Japan. Thirteen odors familiar to Japanese people are used in this test. The OSIT-J is an olfactory discrimination test and is significantly correlated with the average recognition threshold of T & T olfactometry, which is the standard olfactory acuity test used in Japan. In this study, we evaluated the accuracy of the OSIT-J in patients with olfactory disturbances. We compared the OSIT-J and T & T olfactometry results and examined the sensitivity and specificity of the OSIT-J. Using the OSIT-J, olfactory disturbances were diagnosed in more than 70% based on the average recognition threshold determined by T & T olfactometry. OSIT-J is a simple test and is recommended for use in clinical practice for evaluating olfactory disturbances.

Adult↗
PubMed2005

Suppressive activity of vitamin D3 on matrix metalloproteinase production from cholesteatoma keratinocytes in vitro.

There is much evidence that degradation of the extracellular matrix is essential for the development of cholesteatomas and that this is induced by activation of matrix metalloproteinases (MMPs). Vitamin D3 (VD3) has several well-recognised biological activities, including suppression of MMP production. The present study, therefore, was undertaken to examine whether VD3 could suppress MMP production from cholesteatoma keratinocytes in vitro. Keratinocytes (2.5 x 10(5) cells/mL) induced from cholesteatoma tissue specimens were cultured with various concentrations of VD3. After one hour, lipopolysaccharide was added to the cell cultures at 100 mug/mL. The culture supernatants were then collected and assayed for MMP-1 and MMP-3 by ELISA. We also used ELISA to measure the levels of both TIMP (tissue inhibitor of metalloproteinase)-1 and TIMP-2 in culture supernatants. Addition of VD3 into keratinocyte cultures caused the suppression of MMP and TIMP production, which was increased by LPS stimulation. This was dose-dependent. The present results showing the suppressive activity of VD3 on the production of MMPs, which are responsible for tissue remodeling, strongly suggest that VD3 would be a good candidate for an agent in the medical treatment of, or prophylaxis for, cholesteatomas.

Cells, Cultured↗
PubMed2005

Suppression of matrix metalloproteinase production in nasal fibroblasts by tranilast, an antiallergic agent, in vitro.

Allergic rhinitis is an inflammatory disease characterized by nasal wall remodeling with intense infiltration of eosinophils and mast cells/basophils. Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic enzymes that induce airway remodeling. These enzymes are also important in the migration of inflammatory cells through basement membrane components. We evaluated whether tranilast (TR) could inhibit MMP production from nasal fibroblasts in response to tumor necrosis factor-alpha (TNF-alpha) stimulation in vitro. Nasal fibroblasts (NF) were established from nasal polyp tissues taken from patients with allergic rhinitis. NF (2 x 10(5) cells/mL) were stimulated with TNF-alpha in the presence of various concentrations of TR. After 24 hours, the culture supernatants were obtained and assayed for MMP-2, MMP-9, TIMP-1, and TIMP-2 levels by ELISA. The influence of TR on mRNA expression of MMPs and TIMPs in cells cultured for 12 hours was also evaluated by RT-PCR. TR at more than 5 x 10(-5) M inhibited the production of MMP-2 and MMP-9 from NF in response to TNF-alpha stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected. TR also inhibited MMP mRNA expression in NF after TNF-alpha stimulation. The present data suggest that the attenuating effect of TR on MMP-2 and MMP-9 production from NF induced by inflammatory stimulation may underlie the therapeutic mode of action of the agent in patients with allergic diseases, including allergic rhinitis.

Adult↗
PubMed2005

Suppressive activity of epinastine hydrochloride on TARC production from human peripheral blood CD4+ T cells in-vitro.

Thymus- and activation-regulated chemokine (TARC) is an important molecule in the development and maintenance of allergic diseases. However, there is little information about the influence of anti-allergic agents on TARC production. The aim of this study is to examine the influence of epinastine hydrochloride, an H1-receptor antagonist, on TARC production from human peripheral blood CD4+ T cells using an in-vitro cell culture technique. CD4+ T cells prepared from healthy subjects were cultured in wells coated with a combination of OKT3 and anti-CD28 monoclonal antibody in the presence or absence of epinastine HCl for 24 h. The cells were also stimulated with interleukin (IL)-4 in a similar manner. Levels of TARC and IL-4 in culture supernatants were examined by ELISA. The addition of epinastine HCl exerted a dose-dependent suppressive effect on the production of both TARC and IL-4 from CD4+ T cells under co-stimulatory molecule stimulation. The minimum concentration of the agent showing a significant suppressive effect on TARC and IL-4 production was 5.0 microM and 2.5 microM, respectively. Epinastine HCl also suppressed the ability of cells to produce TARC in response to IL-4 stimulation, when the agent was added to cell cultures at more than 2.5 microM. It was concluded that this inhibitory action of epinastine HCl may be partially responsible for epinastine's attenuating effect on allergic diseases.

Adult↗
PubMed2004

Suppressive activity of fexofenadine hydrochloride on thymus- and activation-regulated chemokine production from human peripheral blood leukocytes in response to antigenic stimulation in vitro.

BACKGROUND: Thymus- and activation-regulated chemokine (TARC) is accepted as being an important molecule in the development and maintenance of allergic diseases. However, there is little information about the influence of antiallergic agents on TARC production after allergen challenge. The aim of this study is to examine the influence of fexofenadine hydrochloride (FEX), an H1-receptor antagonist, on TARC production from human peripheral blood leukocytes (PBL) using an in vitro cell culture technique. METHODS: PBL prepared from donors with pollinosis were cultured with either Japanese cedar pollen allergen, Cry j 1, or interleukin (IL)-4 in the presence of various doses of FEX for 6 days. Levels of TARC and the T cell cytokines IL-4 and interferon (IFN)-gamma in culture supernatants were examined by ELISA. RESULTS: FEX did not affect PBL proliferation induced by Cry j 1 stimulation, even when 500 ng/ml of the agent, twice the therapeutic blood levels, was added to cell cultures as assessed by measuring 3H-thymidine incorporation into DNA. On the other hand, FEX at 250 ng/ml (but not 125 ng/ml), similar to therapeutic blood levels, significantly inhibited the ability of PBL to produce IL-4 (but not IFN-gamma), which was enhanced by Cry j 1 stimulation. FEX at concentrations of more than 250 ng/ml also exerted a suppressive effect on TARC production from PBL in response to Cry j 1 and IL-4 stimulation in vitro. CONCLUSION: This inhibitory action of FEX may be partially responsible for the attenuating effect of the agent on allergic diseases.

Adult↗
PubMed2004

Suppressive activity of fexofenadine hydrochloride on the production of eosinophil chemoattractants from human nasal fibroblasts in vitro.

The influence of fexofenadine hydrochloride (FEX; CAS 138452-21-8) on the production of eosinophil chemoattractants, RANTES and eotaxin, from nasal polyp fibroblasts (NPFs) was examined in vitro. Seventh to tenth generation NPFs were cultured with or without 1 microg/ml lipopolysaccharide (LPS) in the presence of various concentrations of FEX. After 24 h, the culture supernatants were obtained and assayed for eosinophil chemoattractants by enzyme-linked immunosorbent assay (ELISA). FEX at a dose of more than 250 ng/ml (but not 100 ng/ml) inhibited RANTES and eotaxin production in response to LPS stimulation, when the agent was added at starting of cell cultures. FEX also showed suppressive effect on RANTES and eotaxin production from NPFs after stimulation with tumor necrosis factor alpha (TNF-alpha). However, the addition of FEX at 12 h after culture could not inhibit factor production. The influence of FEX on messenger RNA (mRNA) expression in NPFs was then examined. The addition of FEX at 100 ng/ml scarcely affected the expression of RANTES and eotaxin mRNA. On the other hand, 250 ng/ ml of FEX significantly inhibited these mRNA expressions that were enhanced by LPS stimulation.

Cells, Cultured↗
PubMed2004

Suppression of matrix metalloproteinase production from nasal fibroblasts by fluticasone propionate in vitro.

OBJECTIVE: To examine the influence of fluticasone propionate (FP) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts in vitro. MATERIAL AND METHODS: Fibroblasts derived from five nasal polyps were stimulated with tumor necrosis factor (TNF)-alpha in the presence of various concentrations of FP. The influence of FP on MMP production was assessed by examining the levels of MMP-2 and -9 in culture supernatants using ELISA. We also examined the influence of FP on MMP mRNA expression using reverse transcriptase polymerase chain reaction. RESULTS: The addition of FP caused significant suppression of MMP-2 and -9 production from nasal polyp fibroblasts in response to TNF-alpha stimulation. MMP mRNA expression was also suppressed by the addition of FP to cell cultures. The minimum concentration of the agent required to cause suppression was 10(-5) M. CONCLUSION: These results suggest that the inhibitory action of FP on tissue remodeling may underlie the clinical efficacy of corticosteroids in nasal polyposis.

Adult↗
PubMed2004

Immunohistochemical localization of eotaxin immunoreactivity in nasal polyps.

Eotaxin is a C-C chemokine that acts to selectively induce local accumulation of eosinophils and basophils. Eotaxin is also believed to be involved in the infiltration of eosinophils in the nasal polyps of patients with chronic sinusitis. However, only a few studies on eotaxin in nasal polyps have been performed. In this study, we investigated the localization of eotaxin in human nasal polyps and the identification of eotaxin-positive cells using immunohistochemistry. The distribution of eotaxin immunoreactivity in the nasal polyps of patients with chronic sinusitis was found to almost coincide with the presence of eosinophils. Eotaxin immunoreactivity was also detected in some vascular endothelial cells. These findings suggest that eotaxin is produced by eosinophils and vascular endothelial cells in nasal polyps and is involved in the accumulation of eosinophils in nasal polyps.

Chemokine CCL11↗
PubMed2004

Suppression of matrix metalloproteinase-9 production from neutrophils by a macrolide antibiotic, roxithromycin, in vitro.

BACKGROUND: Macrolide antibiotics such as erythromycin and roxithromycin (RXM) have an anti-inflammatory effect that may account for their clinical benefit in the treatment of chronic airway inflammatory diseases. However, the precise mechanism of this anti-inflammatory effect is not well understood. PURPOSE: The influence of RXM on matrix metalloproteinase (MMP)-9 production from neutrophils in response to lipopolysaccharide (LPS) stimulation was examined in vitro. METHODS: Neutrophils prepared from normal human peripheral blood (1 x 10(5) cells/ml) were treated with various concentrations of RXM for 1 h, and then stimulated with 1.0 microg/ml of LPS in the presence of the agent for 24 h. MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels in culture supernatants were examined by enzyme-linked immunosorbent assay. RESULTS: Addition of RXM at more than 5.0 microg/ml into cell cultures caused significant suppression of MMP-9 production, which was increased by LPS stimulation. However, the ability of cells to produce TIMP-1 was not affected by RXM treatment, even when the cells were cultured in the presence of agent at 10.0 microg/mL We then examined the influence of RXM on transcriptional factor, nuclear factor-kappaB and activator protein (AP)-1 activation by LPS stimulation. RXM exerted suppressive action on NF-kappaB (P50 and P65) activation when the cells were cultured for 4 h at more than 5.0 microg/ml of the agent. RXM at more than 2.5 microg/ml also suppressed AP-1 (Fra 1 and Jun B) activation in 4-h cultured cells. We finally examined the influence of RXM on MMP-9 mRNA expression in neutrophils. Addition of RXM into cell cultures at more than 5.0 microg/ml caused significant inhibition of mRNA expression, which was enhanced by LPS stimulation for 12 h. CONCLUSION: These results strongly suggest that RXM inhibits neutrophil transmigration into inflammatory sites and results in favorable modification of the clinical status of inflammatory diseases.

Anti-Bacterial Agents↗
PubMed2003

Influence of roxithromycin on inflammatory cytokine production from nasal polyp fibroblasts in vitro.

The influence of macrolide antibiotics, roxithromycin (RXM) and josamycin (JM) on inflammatory cytokine production from human nasal polyp fibroblasts (NPFs) was examined using an in vitro cell culture technique. Addition of RXM at a concentration of 10.0 microg/ml to cell cultures suppressed both IL-6 and RANTES (but not IL-8) production in response to stimulation with 25.0 ng/ml tumor necrosis factor (TNF)-alpha. However, JM could not suppress IL-6, IL-8 and RANTES production from NPFs induced by TNF-alpha stimulation in vitro, even when added to cell cultures at a concentration of 20.0 microgram/ml. In the second part of the study, we examined the influence of RXM on cytokine mRNA expression in NPFs. Addition of RXM at a concentration of 10.0 mg/ml to cell cultures caused reduction of the mRNA expressions of both IL-6 and RANTES, which were enhanced by TNF-alpha stimulation in vitro.

Anti-Bacterial Agents↗
PubMed2003

Suppressive activity of macrolide antibiotics on nitric oxide production from nasal polyp fibroblasts in vitro.

The influence of macrolide antibiotics on nitric oxide (NO) generation was examined using human nasal polyp fibroblasts (NPFs) in vitro. Addition of roxithromycin (RXM) at a concentration of > 7.5 microg/ml to cell cultures was shown to suppress NO production in response to stimulation with 25.0 ng/ml tumor necrosis factor (TNF)-alpha. However, jyosamycin (JM) did not suppress NO production from NPFs induced by TNF-alpha stimulation in vitro, even when added to cell cultures at a concentration of 20.0 microg/ml. We then examined the influence of RXM on inducible nitric oxide synthase (iNOS) mRNA expression in NPFs. Addition of RXM at a dose of 7.5 microg/ml to cell cultures caused reduction of iNOS mRNA expression, which was enhanced by TNF-alpha stimulation in vitro.

Adult↗
PubMed2003

Induction of apoptosis in nasal polyp fibroblasts by glucocorticoids in vitro.

OBJECTIVE: To examine the possible mechanisms underlying the therapeutic mode of action of glucocorticoids (GCs) in nasal polyposis. MATERIAL AND METHODS: The effects of GCs on nasal polyps were firstly evaluated by examining the growth of fibroblasts derived from 10 nasal polyps in vitro. Subsequently, the ability of GCs to induce apoptotic cell death in fibroblasts was examined. RESULTS: Addition of betamethasone 21-phosphate (BET) at a concentration of > 1 x 10(-3) M to cell cultures inhibited cell growth in all cases examined. BET and dexamethasone 21-phosphate, but not testosterone or estradiol, caused apoptotic cell death in 2/10 nasal polyp fibroblasts, as assessed by agarose gel electrophoresis, when the cells were cultured with the agents for > 96 h. The minimum concentration of agent needed to cause apoptosis was 1 x 10(-3) M, which is half of the recommended therapeutic dose. CONCLUSION: The present findings suggest that topical application of GCs in nasal polyposis patients suppresses proliferation of fibroblasts in polyps and results in favorable modification of the clinical status of these patients.

Adult↗
PubMed2003

Suppressive activity of macrolide antibiotics on nitric oxide production by lipopolysaccharide stimulation in mice.

BACKGROUND: Low-dose and long-term administration of macrolide antibiotics into patients with chronic airway inflammatory diseases could favorably modify their clinical conditions. However, the therapeutic mode of action of macrolides is not well understood. Free oxygen radicals, including nitric oxide (NO), are well recognized as the important final effector molecules in the development and the maintenance of inflammatory diseases. PURPOSE: The influence of macrolide antibiotics on NO generation was examined in vivo. METHODS: Male ICR mice, 5 weeks of age, were orally administered with either roxithromycin, clarithromycin, azithromycin or josamycin once a day for 2-4 weeks. The mice were then injected intraperitoneally with 5.0 mg/kg lipopolysaccharide (LPS) and the plasma NO level was examined 6 h later. RESULTS: Although pre-treatment of mice with macrolide antibiotics for 2 weeks scarcely affected NO generation by LPS injection, the administration of macrolide antibiotics, except for josamycin, for 4 weeks significantly inhibited LPS-induced NO generation. The data in the present study also showed that pre-treatment of mice with macrolide antibiotics for 4 weeks significantly suppresses not only production of pro-inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, but also inducible nitric oxide synthase mRNA expressions, which are enhanced by LPS injection. CONCLUSION: These results strongly suggest that suppressive activity of macrolide antibiotics on NO generation in response to LPS stimulation in vivo may, in part, account for the clinical efficacy of macrolides on chronic inflammatory diseases.

Animals↗