Biomedical subjects

K Matsushima

Publications and source records attributed to K Matsushima.

At least 19 recordsLinked to original sources

PubMed2007

Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety.

The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of (111)Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity.

Aged↗

PubMed2006

Overexpression of IL-8 in the cornea induces ulcer formation in the SCID mouse.

AIMS: Although interleukin 8 (IL-8) is not produced in the normal cornea, it has been detected there in several pathological conditions. In this study, the direct effects of IL-8 overexpression on the cornea was examined. METHODS: The corneal surface of severe combined immunodeficiency mice was infected by the adenovirus vector encoding human IL-8 (IL-8/Ad5) and clinical and pathological changes were observed at various time points. RESULTS: Clinically, marked angiogenesis and ulcer formation in the cornea were observed by 12 hours and 24 hours, respectively. Histologically, prominent angiogenesis was observed in the corneal stroma at 12 hours. Cleft formation between the corneal epithelium and stroma, and neutrophil infiltration into the corneal stroma were seen at 16 hours. By 24 hours after the infection with IL-8/Ad5, a shallow ulcer was formed in the cornea. In contrast, infection with the control adenovirus carrying the beta galactosidase gene (LacZ) showed neither corneal ulceration nor neutrophil infiltration. Immunohistochemical analysis showed that infection with IL-8/Ad5 resulted in the production of IL-8 by corneal and conjunctival stromal cells. CONCLUSION: Our results indicate that IL-8 overexpression in corneal tissue causes ulcer formation in the cornea through chemoattraction of neutrophils, suggesting the aetiological role of IL-8 in some types of corneal ulcers.

Adenoviridae↗

PubMed2006

Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that maintains the glomerular and peritubular capillary (PTC) network in the kidney. The soluble form of the VEGF receptor-1 (soluble fms-like tyrosine kinase 1 (sFlt-1)) is known to regulate VEGF activity by binding VEGF in the circulation. We hypothesized that VEGF may be beneficial for maintaining glomerular filtration barrier and vascular network in rats with progressive glomerulonephritis (GN). For blockade of VEGF activity in vivo, rats were transfected twice with plasmid DNA encoding the murine sFlt-1 gene into femoral muscle 3 days before and 2 weeks after the induction of antiglomerular basement membrane antibody-induced GN. Inhibition of VEGF with sFlt-1 resulted in massive urinary protein excretion, concomitantly with downregulated expression of nephrin in nephritic rats. Further, blockade of VEGF induced mild proteinuria in normal rats. Administration of sFlt-1 affected neither the infiltration of macrophages nor crescentic formation. In contrast, treatment of sFlt-1 accelerated the progression of glomerulosclerosis and interstitial fibrosis accompanied with renal dysfunction and PTC loss at day 56. VEGF may play a role in maintaining the podocyte function as well as renal vasculature, thereby protecting glomeruli and interstitium from progressive renal insults.

Animals↗

PubMed2005

A searchable database for proteomes of oral microorganisms.

An online database of proteomes for two-dimensional electrophoresis (2DE) gel data was constructed and it is now freely accessible through a web-based interface. Proteins from three oral bacteria, Streptococcus mutans UA159, Actinobacillus actinomycetemcomitans HK1651, and Porphyromonas gingivalis W83, whose genome databases are freely available, were separated by 2DE, and protein spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and identified. About 1000 spots from the gels of P. gingivalis W83 were extracted and analyzed by MALDI-TOF, and 330 proteins were identified. In addition, 160 of 240 spots of A. actinomycetemcomitans and 158 of 356 spots of S. mutans were identified. Information such as spot coordinates on the gels, protein names (predicted functions), molecular weights, isoelectroric points, and links to online databases, including Oral Pathogen Sequence Databases of the Los Alamos National Laboratory Bioscience Division (ORALGEN) and National Center for Biotechnology Information (NCBI) or The Institute Genomic Research (TIGR), were stored in tables accessible through the relational database management system MySQL on an Apache web server. To test for functionality of this database system, responses of S. mutans to environmental changes were analyzed using the database and 21 spots on the gel were identified as proteins whose expression had been increased or decreased by environmental pH change without in-gel trypsin digestion, protein extraction, or MALDI-TOF/TOF-MS (mass spectrometer) analysis. The identified proteins are agreement with those reported in previous papers on acid tolerance of S. mutans, demonstrating the usefulness of the system. This database is available at http://www.myamagu.dent.kyushu-u.ac.jp/~bioinformatics/index.html or http://www.bipos.mascat.nihon-u.ac.jp/index.html.

Acids↗

PubMed2005

ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.

To clarify the role of disintegrin-like and metalloproteinase with thrombospondin type I motifs-1 (ADAMTS-1) in ovarian function, we examined abnormalities in ovulatory processes, folliculogenesis and the vascular system of ADAMTS-1 null ovaries. First, when immature female mice were treated with pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG), the number of ovulated oocytes was markedly decreased in ADAMTS-1 null mice in comparison to ADAMTS-1 (+/-) controls. The proportion of anovulated follicles to total mature follicles was significantly higher in ADAMTS-1 null females when compared with controls. The numbers of growing follicles at each stage were counted. The number of follicles at type 5b (late preantral) and later stages was markedly reduced in ADAMTS-1 null mice, irrespective of gonadotropin treatment (no gonadotropins, PMSG alone or PMSG/hCG). These data demonstrate that impairment of ovarian function to ovulate oocytes in ADAMTS-1 null mice occurs at two different levels: in the development of growing follicles and ovulatory processes. Furthermore, ADAMTS-1 null ovaries included a number of unusual atretic follicles that showed no sign of oocyte degeneration but lost the surrounding granulosa cell layers and were considered to be derived from type 4 or 5a follicles. These results suggest that ADAMTS-1 is important for follicular development beyond the type 4 and/or 5a and for maintaining normal granulosa cell layers in follicles. Finally, the number of large blood vessels in the medullar zone was significantly decreased in ADAMTS-1 null mice ovaries, suggesting that ADAMTS-1 is also involved in the organization of the medullary vascular network.

ADAM Proteins↗

PubMed2005

"Ring syndrome" involving chromosome 2 confirmed by FISH analysis using chromosome-specific subtelomeric probes.

"Ring syndrome" is described as those cases with complete ring chromosomes showing, independently of the chromosome involved, severe growth failure, minor dysmorphic features, and mild-to-moderate mental retardation, without major malformations. We present a girl with ring 2 chromosome, exhibiting severe growth failure, minor dysmorphic features, spontaneously closed ventricular septum defect, and normal development. G-banding chromosome analysis and fluorescence in situ hybridization (FISH) analysis using chromosome-specific subtelomeric probes (2ptel, 2qtel) demonstrated the major karyotype as 46,XX,r(2)(p25.3q37.3).ish r(2)(2ptel+,2qtel+). We review the cases with "ring syndrome" confirmed by FISH using chromosome-specific subtelomeric probes, suggesting that this method might be useful to predict developmental prognosis in a case with an apparently complete ring chromosome.

Chromosome Banding↗

PubMed2004

Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2.

BACKGROUND: Both prostaglandin (PG) D receptor (DP) and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells)/DP2 are high-affinity receptors for PGD2. Previous studies have demonstrated that PGD2 enhances releasability and induces CRTH2/DP2-mediated migration in human basophils, but the precise effects of PGD2 on basophils as well as receptor usage have not been fully clarified. OBJECTIVE: We comprehensively explored the roles of DP and CRTH2/DP2 in basophil functions by using selective agonists and antagonists for each receptor. METHODS: DP and CRTH2/DP2 transcripts were quantified by real-time PCR. We studied the effects of selective agonists (DP: BW245C; CRTH2/DP2: 13,14-dihydro-15-keto (DK)-PGD2) and/or antagonists (DP: BWA868C; CRTH2/DP2: ramatroban) on Ca2+ mobilization, migration, degranulation, CD11b expression and survival of human basophils. RESULTS: Basophils expressed transcripts of both DP and CRTH2/DP2, but the levels of CRTH2/DP2 transcripts were ca. 100-fold higher compared with DP transcripts. Ca2+ influx was induced in basophils by either PGD2 or DK-PGD2/CRTH2 agonist but not by BW245C/DP agonist. Basophils treated with PGD2 were completely desensitized to subsequent stimulation with DK-PGD2, but not vice versa. DK-PGD2 as well as PGD2 up-regulated CD11b expression, induced migration and enhanced degranulation, and those effects were completely antagonized by ramatroban/CRTH2 antagonist. In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE-mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist. On the other hand, while PGD2 significantly shortened the basophil life-span, neither DK-PGD2/CRTH2 agonist nor BW245C/DP agonist did. CONCLUSION: CRTH2/DP2 is primarily responsible for the pro-inflammatory effects of PGD2 on human basophils, while DP introduces negative signals capable of antagonizing the effects of CRTH2/DP2 in these cells. The effects of PGD2 on longevity imply a mechanism(s) other than via DP or CRTH2/DP2. CRTH2/DP2 on basophils may afford opportunities for therapeutic targeting in allergic inflammation.

Basophils↗

PubMed2004

CCL22 and CCL17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis.

Pulmonary fibrosis is caused by various known and unknown aetiologies, but the key pathogenic mechanisms are still ill-defined. Chemokines are a large family of chemotactic cytokines that play pivotal roles in various inflammatory diseases. In the present study, the roles of chemokines in a rat model of radiation pneumonitis/ pulmonary fibrosis were examined. Accumulation of inflammatory cells and pneumonitis were observed on day 28, and diffuse alveolar wall thickening with extensive fibrosis was observed on day 56. In addition to the previously reported CCL2 (macrophage chemoattractant protein-1) induction, selective upregulation of CCL22 (macrophage-derived chemokine) and CCL17 (thymus and activation-regulated chemokine) were demonstrated for the first time in the irradiated lung tissues. Immunohistochemically, it was demonstrated that CCL22 and CCL17 were localised primarily to alveolar macrophages, whereas their receptor CC chemokine receptor 4 (CCR4) was detected on alveolar lymphocytes and macrophages. On further analysis of bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis and sarcoidosis, elevated levels of CCL22, but not of CCL17, were observed in the idiopathic pulmonary fibrosis patients. Since these two chemokines play pivotal roles in various type-2 T-helper cell-dominant diseases, it was speculated that CCL22, and probably CCL17, are involved in the pathophysiology of radiation pneumonitis/pulmonary fibrosis and idiopathic pulmonary fibrosis through the recruitment of CC chemokine receptor 4-positive type-2 T-helper cells and alveolar macrophages.

Aged↗

PubMed2003

Accumulation of CCR4-expressing CD4+ T cells and high concentration of its ligands (TARC and MDC) in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia.

BACKGROUND: Th2 cells are thought to be involved in eosinophilic inflammation of the lung. CC chemokine receptor 4 (CCR4) has been identified as a specific receptor for both thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), and is preferentially expressed on Th2 cells. OBJECTIVE: Our aim was to evaluate the role of Th2 cells in the lung of patients with eosinophilic pneumonia (EP). METHODS: The concentrations of TARC, MDC, and interleukin (IL)-5 were measured in bronchoalveolar lavage fluid (BALF) by ELISA. Proportion of CCR4-expressing CD4+ T cells (CCR4+ CD4+ T cells) was determined by flow cytometry. RESULTS: TARC and MDC concentrations in BALF were higher in patients with EP than in normal subjects. The proportion of CCR4-expressing cells among CD4+ T cells was higher in BALF than in peripheral blood of patients with EP. There was a significant correlation between the number of CCR4+ CD4+ T cells and the levels of TARC, MDC, and IL-5 in BALF of patients with EP. CONCLUSIONS: Our data suggest that Th2 cells, which express CCR4 and its ligands (TARC and MDC), contribute to the pathogenesis of EP in the lung.

Adult↗

PubMed2003

High level of thymus and activation-regulated chemokine in blister fluid and sera of patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by eosinophilia and high serum IgE levels. The accumulated evidence suggests that various cytokines are involved in the lesional skin of patients with BP. Recently, thymus and activation-regulated chemokine (TARC/CCL17), a CC chemokine, was identified as a selective chemoattractant for CC chemokine receptor 4 (CCR4)-expressing cells. OBJECTIVE: In this study, we examined the involvement of TARC in patients with BP. METHODS: We determined the fluid and serum TARC levels in patients with BP by enzyme-linked immunosorbent assay and compared the serum TARC levels with the eosinophil numbers in peripheral blood. We also compared the serum TARC levels in five patients with BP before and after they were treated. Moreover, we examined TARC, CCR4 and CXC chemokine receptor 3 (CXCR3) expression in the lesional skin of patients with BP by immunohistochemical procedures. Furthermore, we measured CCR4 positivity in CD4+ CD45RO+ cells of peripheral blood mononuclear cells (PBMCs) in patients with BP and healthy control subjects. RESULTS: The fluid TARC levels in patients with BP were significantly higher than those in blisters from burn patients or suction blisters of healthy control subjects. The serum TARC levels in patients with BP were also significantly higher than those in pemphigus vulgaris (PV) patients and healthy control subjects, and decreased after the treatment. The serum TARC levels in patients with BP significantly correlated with the eosinophil numbers in peripheral blood (r = 0.72, P < 0.002). Immunohistochemistry showed a strong reactivity of TARC in the epidermal keratinocytes (KCs) of BP. Moreover, both CCR4 and CXCR3 were expressed on the dermal infiltrating CD4+ T cells mainly beneath the bullae of patients with BP. Fluorescence-activated cell sorting analysis showed a higher percentage of CCR4 positivity in CD4+ CD45RO+ cells of PBMCs in patients with BP than that in healthy control subjects, while there was no significant difference of CXCR3 positivity in CD4+ CD45RO+ cells of PBMCs between patients with BP and healthy control subjects. CONCLUSIONS: These findings strongly suggest that TARC may be one of the important chemokines that are involved in the pathogenesis of BP.

Adult↗

PubMed2003

CCR4 is an up-regulated chemokine receptor of peripheral blood memory CD4+ T cells in Crohn's disease.

Several chemokine receptors are expressed selectively on the surface of T cells depending on their polarization. The aim of this study was to characterize chemokine receptor expression in peripheral blood memory T cells in Crohn's disease (CD) and ulcerative colitis (UC), and to correlate the expression with disease activity. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with CD, 30 patients with UC, 24 normal controls and 10 disease controls. PBMCs were stained by anti-CCR3, CCR4, CCR5, CXCR3, CD4, CD8, CD45RO and beta 7 integrin, and the expression of the chemokine receptors were determined by flow cytometry. CCR4 expression on memory T cells was significantly lower in UC than in CD or normal controls, and that of memory CD4+ T and beta 7(high) memory CD4+ T cells was significantly higher in CD than in UC or normal controls. CCR4 expression on memory CD4+ T cells exhibited significant positive correlation with disease activity in CD, and this decreased significantly after treatment. Such a decrease was not found in the disease controls. CCR5 and CXCR3 expression on memory CD8+ T cells was significantly lower in CD than in normal controls. CXCR3 expression on beta 7(high) memory CD4+ T and CXCR3 expression on memory CD8+ T cells were lower in UC than in normal controls. These findings suggest that in peripheral blood memory T cells, chemokine receptor expression is different between CD and UC. Enhancement of CCR4 and suppression of CCR5 and CXCR3 seem to be the characteristic chemokine receptor profile in peripheral blood memory T cells of CD.

Acute Disease↗

PubMed2003

Circulating lymphocyte subsets linked to intracellular cytokine profiles in normal humans.

To determine whether there is an association between intracellular cytokine profiles and the expression of surface antigens, we performed a simultaneous flow cytometric analysis of these laboratory parameters in 11 healthy volunteers. Peripheral blood lymphocytes were double-stained for CD4 or CD8, as well as CD11a, CD25, CD26, CD29 and CD45RA or the chemokine receptors CCR3, CCR4, CCR5 or CXCR3. Portions of the cell samples were cultured for 4 h in the presence of 1 microm monensin and 20 microg/ml brefeldin A with or without stimulation by phorbol myristate acetate plus ionomycin for the detection of intracellular interferon-gamma (IFN-gamma), interleukin-2 (IL-2), tumour necrosis factor (TNF)-alpha, and IL-4. As a result, CD4+CD29high helper inducer T cells were closely associated with IFN-gamma and TNF-alpha producing CD4+ cells, while CD4+CXCR3+ cells showed a negative correlation with IL-4-producing cells, suggesting that both of these CD4+ subsets consist mainly of Th1 cells. In contrast, CD4+CD45RA+ cells were correlated inversely with IFN-gamma and TNF-alpha-producing cells, and CD8+CD11ahigh killer effector and total CCR5+ cells showed an inverse correlation with IL-2 producing cells, suggesting an immunoregulatory role for these three subsets in non-pathological conditions. Therefore, monitoring of lymphocyte subsets that express functional surface antigens could provide additional information concerning immune deviation, as assessed by the production of Th1/Th2 type cytokines. Further, this type of combined study may provide clues for the pathogenesis of immune-mediated disorders.

Adult↗

PubMed2002

Increased levels of a TH2-type CC chemokine thymus and activation-regulated chemokine (TARC) in serum and induced sputum of asthmatics.

BACKGROUND: Cytokines liberated by TH2 cells play crucial roles in the pathogenesis of bronchial asthma. Recent studies have demonstrated that CC chemokine receptor (CCR)4 is preferentially expressed by TH2 cells. These facts suggest possible involvement of two CCR4-specific ligands i.e., thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), in the pathogenesis of bronchial asthma via recruitment of TH2 cells to inflammatory sites. We investigated the levels of TARC and MDC in the serum and induced sputum of asthmatics. METHODS: The levels of TARC in the serum (46 asthmatics and 26 healthy subjects) and induced sputum (30 asthmatics and 6 healthy subjects) were measured using a highly sensitive ELISA system. The levels of eotaxin and MDC were also measured by ELISA. RESULTS: TARC, but not MDC, was significantly increased in asthmatic sera (P<0.001). Although MDC was undetectable in the sputum of most cases by our assay system, sputum TARC was significantly increased (P=0.027). CONCLUSIONS: The elevated TARC levels in asthmatics might be involved in the pathophysiology of asthma.

Adult↗

PubMed2002

Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis: up-regulation of C-C chemokine receptor 4 in atopic dermatitis.

BACKGROUND: Th2 and Th1 cells have been suggested to express CCR3/CCR4 and CCR5/CXCR3, respectively. OBJECTIVE: We examined CCR3, CCR4, CCR5 and CXCR3 expression and cytokine production in peripheral blood CD4+ T cells from patients with atopic dermatitis (AD), which has been postulated to be a Th2-type cell-mediated disease, and then analysed the possible correlation between these values and the levels of several clinical parameters. METHODS: Intracellular cytokine production and chemokine receptor expression in peripheral blood CD4+ T cells from 40 AD patients and 20 sex- and age-matched healthy control subjects were studied by flow cytometry. RESULTS: The frequencies of IL-4- and IL-13-producing CD4+ T cells from patients with AD were significantly higher than those from healthy control subjects (IL-4:3.9 +/- 2.1% vs. 1.6 +/- 0.7%, P = 0.0005, IL-13:4.0 +/- 2.1% vs. 1.8 +/- 0.8%, P = 0.0023), whereas the frequencies of IL-2- and IFN-gamma-producing CD4+ T cells were significantly decreased in AD patients (IL-2:38.1 +/- 10.3% vs. 51.3 +/- 6.3%, P = 0.0003, IFN-gamma: 9.9 +/- 3.5% vs. 26.4 +/- 4.6%, P < 0.0001). The percentage of CCR4+ cells in CD4+ CD45RO+ T cells in AD patients was significantly higher than that in healthy control subjects (24.4 +/- 8.0% vs. 10.9 +/- 2.3%, P < 0.0001) and was correlated positively with the total serum IgE, serum lactic dehydrogenase (LDH) level, eosinophil number, eruption score, and IL-4 and IL-13 secretion in CD4+ T cells, and inversely with IL-2 and IFN-gamma secretion in CD4+ T cells. In contrast, CCR3 was not detected on circulating CD4+ T cells even in AD patients. On the other hand, the percentage of CCR5+ or CXCR3+ cells in CD4+ CD45RO+ T cells in AD patients was significantly decreased (CCR5:23.2 +/- 7.0% vs. 28.4 +/- 5.4%, P = 0.023, CXCR3:29.9 +/- 11.4% vs. 38.5 +/- 6.7%, P = 0.028) and was positively correlated with eruption score (P < 0.05). Multiple regression analyses showed that the percentage of CCR4 expression highly correlated with serum IgE, LDH, eosinophil number and eruption in AD patients. CONCLUSION: CCR4+ cells might be involved in the aetiopathogenesis of AD.

Adolescent↗

PubMed2001

Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma.

BACKGROUND: Macrophages often infiltrate into solid tumor tissues. Tumor-associated macrophages (TAMs) are known to play a crucial role in tumor progression. Monocyte chemoattractant protein-1 (MCP-1) is one of the major chemokines capable of inducing chemotactic migration of monocytes. METHODS: With the objective of investigating the clinical significance of MCP-1, the authors analyzed the expression of MCP-1 and of some other molecules by immunohistochemistry in 230 samples of primary breast carcinoma tissue. MCP-1 staining was performed using an anti-MCP-1 monoclonal antibody, and it was assessed by grading the percentage of stained cells. RESULTS: It was found that 117 breast tumor specimens (51%) had intensive staining in tumor cells. The expression of MCP-1 in tumor cells had a significant correlation with the expression of thymidine phosphorylase and membrane type 1-matrix metalloproteinase. In addition, MCP-1 expression tended to be associated with the accumulation of TAMs, which were counted by CD68 staining, and with microvessel density. MCP-1 expression in TAMs was correlated significantly with the histologic vessel invasion of tumor cells. CONCLUSIONS: The results of this study suggest that MCP-1 may play key roles in macrophage recruitment, in the expression of angiogenic factors, and in the activation of matrix metalloproteinases in patients with breast carcinoma.

Angiogenesis Inducing Agents↗

PubMed2001

Effects of oral steroids on blood CXCR3+ and CCR4+ T cells in patients with bronchial asthma.

Corticosteroids are widely used in bronchial asthma, but their mechanism of action is not fully understood. The in vitro studies have proposed that human T helper cells, type 1 (Th1) favor expression of CXCR3, whereas Th2 cells favor CCR4. In this study we investigated whether oral prednisolone modulates the balance of peripheral blood CXCR3+ and CCR4+ T cells. We analyzed the T-cell subsets in 28 patients with stable atopic asthma and 13 normal control subjects before and after 2 wk of treatment with prednisolone, 20 mg/d, or placebo in a randomized, double-blind, parallel group study. The numbers of CXCR3+ and CCR4+ memory T cells were measured with a flow cytometer, and expressed as percentages in CD4+/CD45RO+ memory T cells. In the steroid-treated asthma group, there was a decrease in CCR4+ T cells (from 29.3% to 20.3%, p < 0.0001), and an increase in CXCR3+/ CCR4+ ratio (from 1.86 to 2.89, p = 0.0047), whereas there was no change in CXCR3+ T cells. However, the percentages of CCR4+ cells did not change after steroid therapy in normal control subjects. These results suggest that short-term oral corticosteroid modulates the balances of CXCR3+ and CCR4+ cells in patients with asthma.

Administration, Oral↗

PubMed2001

A critical role for mouse CXC chemokine(s) in pulmonary neutrophilia during Th type 1-dependent airway inflammation.

Ag-specific Th1 and Th2 cells have been demonstrated to play a critical role in the induction of allergic diseases. Here we have investigated the precise mechanisms of Th1-induced airway inflammation. Airway inflammation was induced in BALB/c mice by transfer of freshly induced OVA-specific Th1 or Th2 cells followed by OVA inhalation. In this model, both Th1 and Th2 cells induced airway inflammation. The former induced neutrophilia in airways, whereas the latter induced eosinophilia. Moreover, we found that Th1 cells induced more severe airway hyperresponsiveness (AHR) than Th2 cells. The eosinophilia induced by Th2 cell infusion was almost completely blocked by administration of anti-IL-5 mAb, but not anti-IL-4 mAb. In contrast, Th1-induced AHR and pulmonary neutrophilia were inhibited by the administration of anti-human IL-8R Ab, which blocks the function of mouse CXC chemokine(s). These findings reveal a critical role of mouse CXC chemokine(s) in Th1-dependent pulmonary neutrophilia and AHR.

Administration, Inhalation↗

PubMed2001

Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells.

The use of tumor cells as vaccines in cancer immunotherapy is critically dependent on their capacity to initiate and amplify tumor-specific immunity. Optimal responses may require the modification of the tumor cells not only to increase their immunogenicity but also to improve their ability to recruit effector cells to the tumor sites or sites of tumor antigen exposure. It has been reported that CD40 cross-linking of acute lymphoblastic leukemia (ALL) cells significantly increases their immunogenicity and allows the generation and expansion of autologous antileukemia cytotoxic T lymphocytes. This study demonstrates that the CD40 ligation of these tumor cells also induces the secretion of the CC-chemokines MDC and TARC. Supernatants from malignant cells cultured in the presence of sCD40L promote the migration of activated T cells that express CCR4, the common specific receptor for MDC and TARC. More importantly, the supernatants from CD40-stimulated tumor cells also support the transendothelial migration of autologous CCR4(+) antileukemia T cells. Therefore, the results demonstrate that the delivery to leukemia cells of a single physiologic signal, that is, CD40 cross-linking, simultaneously improves tumor cell immunogenicity and induces potent chemoattraction for T cells. (Blood. 2001;98:533-540)

Antigen Presentation↗