Research Interests:
The high-affinity receptor for IgE (Fc epsilon R I) has a tetrameric structure composed of one alpha, one beta and two disulfide-linked gamma subunits (alpha beta gamma 2), of which alpha subunit binds IgE with high affinity and beta,... more
The high-affinity receptor for IgE (Fc epsilon R I) has a tetrameric structure composed of one alpha, one beta and two disulfide-linked gamma subunits (alpha beta gamma 2), of which alpha subunit binds IgE with high affinity and beta, gamma subunits transduce intracellular activation signals. We generated recombinant soluble form of the ectodomain of the human Fc epsilon R I alpha subunit (soluble alpha) and monoclonal antibodies again Fc epsilon R I alpha which inhibit IgE-binding. Soluble alpha works not only as a prophylactic agent for allergy but is also effective for on-going allergic reaction. In addition soluble alpha was elucidated to bind to membranous IgE on B cells and inhibit IgE synthesis. Fab fragments of the monoclonal Abs which inhibit IgE-binding were also very effective as anti-allergic agents and humanization of these Abs are underway.
Research Interests:
Research Interests:
ABSTRACT
Research Interests:
Combined treatment with anti-leukocyte function-associated antigen-1 (LFA-1) and anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies leads to allograft tolerance in murine cardiac transplantation. In the present study,... more
Combined treatment with anti-leukocyte function-associated antigen-1 (LFA-1) and anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies leads to allograft tolerance in murine cardiac transplantation. In the present study, we analyzed the mechanisms for this tolerance induction. In the tolerant mice, proliferative response of splenic T cells against donor-type cardiac myocytes and of CD8+ T cells against donor-type alloantigens was impaired as compared with responses in naive or rejected mice, but was completely restored with exogenous interleukin 2. This suggests that class I-restricted CD8+ T cells of tolerant mice were rendered anergic against donor-type alloantigens in the periphery. In contrast, proliferative response of CD4+ T cells against donor-type alloantigens in vitro was comparable between tolerant and naive mice. When heart and skin grafts from the same donor (BALB/c [H2d]) were simultaneously transplanted to C3H mice (H2k), both were rejected within 29 days, even though the mice were similarly treated with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies. In contrast, when heart graft from BALB/c and skin graft from third-party donor (C57BL/6 [H2b]) were simultaneously transplanted to C3H mice under the same condition, the heart graft was accepted indefinitely and the skin graft was rejected. These findings suggest that the peripheral tolerance against cardiac allografts could be induced by selective inactivation of alloreactive CD8+ T cells resulting from the lack of cognate help by CD4+ T cells.
Research Interests:
Research Interests:
Research Interests:
NC/Nga mouse is well known as a mouse model for atopic dermatitis. In general, when NC/Nga mouse are raised under specific pathogen free (SPF) conditions no skin lesions are detected, but when under non-filtrated (conventional) condition,... more
NC/Nga mouse is well known as a mouse model for atopic dermatitis. In general, when NC/Nga mouse are raised under specific pathogen free (SPF) conditions no skin lesions are detected, but when under non-filtrated (conventional) condition, atopic dermatitis like skin lesions appear spontaneously. However, this dermatitis develops in 70-90% of mice (not 100%), which makes it difficult to perform reproducible experiments every time. This study was performed under SPF conditions, using the four solutions (2% SDS, 4% SDS, ethanol, acetone/ether) to destroy the skin barrier function, and thereafter, applying the extracted solution of mite: Dermatophagoides pteronyssinus, which is a very popular antigen in pathogenesis of human atopic dermatitis. The extracted solution of mite was applied repeatedly on the NC/Nga mice with a pretreatment of barrier destroying solution and after 8 weeks the mice developed severe dermatitis (clinical skin condition score of 7-10.2 points) with marked elevation of plasma IgE level, whereas mice coated only with the barrier destroying solution showed weak skin lesion with no elevation of plasma IgE level. BALB/c mice, which are employed as control, showed weak skin lesion (clinical skin condition score of 0-3.8 points) and slight elevation of plasma IgE level after repeated application of the extracted solution of mite with a pretreatment of the barrier destroying solution, whereas mice coated only with the barrier destroying solution showed weak skin lesion and the no elevation of plasma IgE level was observed. In this study, using several solutions to disturb the skin barrier function before applying the antigen, we have found a suitable condition and types of solutions in inducing dermatitis in NC/Nga mice.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Nephrology, Skeletal muscle biology, Magnetic Resonance Imaging, Kidney diseases, Cytokines, and 56 moreVitamin D, Calcium, Japan, Hemoglobinopathies, Diarrhea, Tuberculosis, Humans, Aquaporins (AQP), Mycobacterium tuberculosis, Glucose, Kidney, Insulin, Diabetes mellitus, Mutation, Female, Animals, Male, DNA fingerprinting, Pedigree, Hypopituitarism, Behavioral Animal Models, T lymphocytes, Microdialysis, Middle Aged, Molecular cloning, ALOPECIA, Pulmonary Medicine, Isoenzymes, Aquaporin, Prognosis, Medical Electronics, Potassium Channels, Oximetry, Disease Progression, Porphyrias, Rabbits, Amino Acid Sequence, Pulmonary Tuberculosis, Erythrocyte Membrane, Type 2 Diabetes Mellitus, Erythrocytes, Chronic Kidney Failure, Equipment Design, Syndrome, Respiratory Sounds, Lymphocytosis, Biosensing Techniques, Autoantibodies, Amyloidosis, Glutamate decarboxylase, Renal Dialysis, islets of Langerhans, Adenosine Triphosphate, Molecular Sequence Data, spasm, and Hypersensitivity Delayed
Transforming growth factor beta (TGF-beta) has been suggested to play an important role in the development of airway remodeling in asthma; this suggestion is based on evidence that expression levels of TGF-beta are correlated with unique... more
Transforming growth factor beta (TGF-beta) has been suggested to play an important role in the development of airway remodeling in asthma; this suggestion is based on evidence that expression levels of TGF-beta are correlated with unique parameters of airway remodeling, such as thickness of basement membrane. However, the relevant studies were inconclusive because they were unable to demonstrate active signaling mediated by the cytokine in the airways of asthmatic individuals. We sought to determine whether TGF-beta signaling was active in the airways of asthmatic subjects and, if so, whether it was correlated with clinicopathologic features associated with the development of airway remodeling in asthma. We examined the phosphorylation status of Smad2 in bronchial biopsy samples obtained from 40 asthmatic subjects as a marker of active TGF-beta signaling, and we studied its correlation with basement membrane thickness. Expression levels of phosphorylated Smad2 in bronchial biopsy specimens from asthmatic subjects were higher than those in specimens from normal subjects, and they were correlated with basement membrane thickness in asthma. The findings provide evidence that TGF-beta signaling was active in asthmatic airways and that the activity was associated with the development of airway remodeling in asthma.
Research Interests:
Research Interests:
Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the... more
Helicobacter pylori (H. pylori) induces severe inflammation and plays a key role in gastric mucosal diseases. In general, mast cells have been believed to play an important role in inflammation. Although mast cells were detected in the gastric mucosa, the role of mast cells in the gastric mucosal inflammation caused by H. pylori is still unclear. Therefore, we examined the effects of H. pylori water extract on the degranulation of mast cells to clarify the role of these cells in gastric mucosal inflammation induced by H. pylori. Mast cells prepared from rat abdominal cavity were incubated with H. pylori for 30 min. The protein concentrations of H. pylori water extract used in this study were 0.5-3 mg/ml. The degranulation of mast cells were monitored morphologically by phase contrast microscopy equipped with time-lapse video recording system and biochemically by measuring histamine and beta-hexosaminidase. H. pylori water extract induced the degranulation of mast cells dose-dependently. The identical experiment was performed without extracellular calcium, and no significant degranulation was found. The data indicates that the degranulation of mast cells by H. pylori water extract depend on extracellular calcium. The present results indicate that H. pylori might be involved in the gastric mucosal inflammation as a trigger of mast cell degranulation for releasing chemical mediators.
Research Interests:
Research Interests:
Research Interests:
ABSTRACT
Research Interests:
Cross-linkage of the high affinity Fcepsilon receptors (FcepsilonRI) on the surface of the mast cell by the allergen-IgE complex is a central event in the induction of allergic inflammatory reactions. However, the precise roles of human... more
Cross-linkage of the high affinity Fcepsilon receptors (FcepsilonRI) on the surface of the mast cell by the allergen-IgE complex is a central event in the induction of allergic inflammatory reactions. However, the precise roles of human mast cells in the perpetuation of allergic inflammation is not well known. IL-13 plays an important role in the regulation of allergic inflammation, especially being involved in the induction of IgE synthesis. We investigated whether human lung mast cells have the capacity to produce IL-13 by cross-linking of the FcepsilonRI. Lung mast cells were purified by affinity magnetic selection with monoclonal antibody YB5.B8 against c-kit to achieve a final mast cell purity of more than 93%. Purified mast cells were precultured with human myeloma IgE (3 microg/mL) for 16 h before challenge with stem cell factor (SCF) (50 ng/mL) and anti-IgE (1 microg/mL). By RT-PCR, ELISA and immunocytochemistry, we evaluated the capacity of human lung mast cells to express and produce IL-13. IgE-dependent activation of human lung mast cells caused an increase in IL-13 mRNA expression which persisted for up to 12 h. Immunoreactive IL-13 was detectable 24 h after activation of sensitized lung mast cells with SCF and anti-IgE in 6 of 13 non-asthmatic donors and a million of mast cells secreted 106.7 +/- 42.65 (mean +/- SE) pg of IL-13 into the culture supernatants. SCF alone induced 61.63 +/- 31.12 pg of IL-13 from 106 mast cells. This difference was statistically significant (P = 0.028, n = 13). Furthermore, we confirmed by immunocytochemistry that immunological activation induced an increase of intracellular IL-13. These findings demonstrate the capacity of human lung mast cells to transcribe IL-13 after IgE-dependent activation and to synthesize and release IL-13.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The activation of liver X receptor (LXR) α or LXRβ negatively regulates the expression of pro-inflammatory genes in mammalian cells. We recently reported that 25-hydroxycholesterol, a representative LXR-activating oxysterol, suppresses... more
The activation of liver X receptor (LXR) α or LXRβ negatively regulates the expression of pro-inflammatory genes in mammalian cells. We recently reported that 25-hydroxycholesterol, a representative LXR-activating oxysterol, suppresses IL-6 production in mouse mast cells (MCs) following its engagement of the high-affinity IgE receptor (FcεRI). This finding suggests that murine MCs express functional LXRs; however, the mechanisms underlying the LXR-dependent repression of the MC-mediated production of pro-inflammatory cytokines, including IL-6, are poorly understood. Therefore, we employed the synthetic LXR ligand GW3965 to examine the functions of LXRα and LXRβ in the production of pro-inflammatory cytokines by murine bone marrow-derived MCs (BMMCs). We prepared BMMCs from wild-type (WT), LXRα(-/-), and LXRα/β(-/-) mice. Each group of BMMCs was pretreated with GW3965 and then stimulated with IgE+antigen (Ag) or lipopolysaccharide (LPS). Cytokine production was then analyzed using specific ELISA kits. The activation of LXRs by GW3965 significantly attenuated the production of IL-1α and IL-1β, but not of IL-6, in the WT and LXRα(-/-) BMMCs stimulated with IgE+Ag. However, GW3965 treatment decreased the production of IL-1α, IL-1β, and IL-6 in WT and LXRα(-/-) BMMCs upon stimulation with LPS, while the GW3965-mediated suppression of cytokine production was nearly absent from the LXRα/β(-/-) BMMCs. These findings demonstrate, for the first time, that the activation of LXRs by GW3965 attenuates the antigen- or LPS-induced production of pro-inflammatory cytokines, such as IL-1α and IL-1β, in murine MCs and that LXRβ plays an important role in the LXR-mediated repression of cytokine production.
Research Interests:
Summary Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of... more
Summary Natural killer (NK) cells exhibit cytotoxicity against variety of tumor cells and virus-infected cells without prior sensitization and represent unique lymphocytes involved in primary host defense. NKR-P1 is thought to be one of NK receptors mediating activation signals because cross-link- ing of NKR-P1 activates NK cells to exhibit cytotoxicity and IFN- g production. However, molecular mechanism of NK cell
Research Interests:
Omalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. To measure active IgE levels in sera from patients treated with omalizumab, the IgE subfraction in complex with... more
Omalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. To measure active IgE levels in sera from patients treated with omalizumab, the IgE subfraction in complex with omalizumab should be eliminated from total IgE, and free IgE levels can then be determined. With the aim of therapeutic monitoring for anti-IgE therapy, we developed a new ELISA for free IgE. We used recombinant human soluble FcεRIα as a capture antigen and a biotinylated polyclonal anti-IgE antibody for detection. Using the newly developed ELISA, we measured the serum free IgE levels weekly in four asthmatic patients after their first omalizumab injection. We also measured the serum free IgE levels in 54 patients treated with omalizumab for over 4 weeks. This assay was technically robust, the mean recovery rate in serum was 93.16% ± 5.34%. For all patients, omalizumab treatment significantly reduced serum free IgE levels prior to the second omalizuma...
Research Interests:
Research Interests:
Research Interests:
Engagement of the high-affinity IgE receptor (FcεRI) can be either protective or non-protective against apoptotic cell death (ACD) in bone marrow-derived murine mast cells (BMMCs) after IL-3 withdrawal, depending on the avidity between... more
Engagement of the high-affinity IgE receptor (FcεRI) can be either protective or non-protective against apoptotic cell death (ACD) in bone marrow-derived murine mast cells (BMMCs) after IL-3 withdrawal, depending on the avidity between IgE and its antigen. We recently reported that protein L (PpL), a bacterial Igκ-binding soluble protein, is able to stimulate intracellular signaling to induce activation of BMMCs by interacting with the IgEκ-FcεRI complex. However, it is unclear if cross-linking of FcεRI with IgEκ and PpL prevents or enhances IL-3-dependent ACD in BMMCs. In the present study, we found that IL-3-dependent ACD of BMMCs is accelerated by loading soluble PpL in the presence of IgEκ-occupied FcεRIα. For this purpose, soluble PpL was incorporated into the BMMCs. Unlike soluble PpL, immobilized PpL failed to enhance ACD, although both forms of PpL induced IL-6 production equally in BMMCs. In addition, we observed that DNS5-BSA protected anti-DNS IgE-sensitized BMMCs from IL...
Research Interests:
The process of sensitisation by specific contact allergens is indispensable for the induction of allergic contact dermatitis. Oxazolone is a well-characterised contact allergen. Previous studies suggested that immune cells bearing the... more
The process of sensitisation by specific contact allergens is indispensable for the induction of allergic contact dermatitis. Oxazolone is a well-characterised contact allergen. Previous studies suggested that immune cells bearing the FcRγ subunit are essential for oxazolone-induced contact hypersensitivity, but the biological functions of the FcRγ subunit in the process of sensitisation to oxazolone remain unknown. In this study, we show that FcRγ deficiency decreases ear-swelling responses to oxazolone in mice. However, we found that oxazolone-sensitised FcRγ(-/-) mice and oxazolone-sensitised wild-type (WT) mice have comparable numbers of CD11c(+) MHCII(hi) dendritic cells (DCs) in their draining lymph nodes (LNs). In addition, oxazolone-sensitised LN cells from both FcRγ(-/-) and WT mice showed considerable production of interferon-gamma (IFNγ), interleukin-4 (IL-4) and IL-17A upon oxazolone-keyhole limpet haemocyanin loading. Consistent with these data, oxazolone-sensitised FcR...
Research Interests:
CCAAT/enhancer binding protein alpha (C/EBPα) is a transcription factor that influences immune cell fate and differentiation. However, the effect of C/EBPα on mast cells is not fully understood. In this study, we showed that C/EBPα... more
CCAAT/enhancer binding protein alpha (C/EBPα) is a transcription factor that influences immune cell fate and differentiation. However, the effect of C/EBPα on mast cells is not fully understood. In this study, we showed that C/EBPα suppressed granule formation in mast cells and increased macrophage inflammatory protein (MIP)-2 production from mast cells upon bacterial stimulation. These results indicate that C/EBPα regulates the balance between the allergic response and the innate immune response of mast cells. Furthermore, we showed that stimulation of mast cells with the Lactobacillus casei JCM1134(T) strain during late differentiation up-regulated C/EBPα expression in differentiated mast cells. This suggests that intestinal commensal bacteria modulate C/EBPα expression and thereby regulate mast cell function.
Research Interests:
Intracellular reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O2()) are thought to mediate apoptosis induced by death receptor ligands, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). However, the... more
Intracellular reactive oxygen species (ROS) such as hydrogen peroxide (H(2)O2()) are thought to mediate apoptosis induced by death receptor ligands, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). However, the role of H(2)O(2) is controversial, since some evidence suggests that H(2)O(2) acts as an anti-apoptotic factor. Here, we show that exogenously applied H(2)O(2) (30-100 µM) induces cell death in TRAIL-resistant human melanoma cells via intracellular superoxide (O(2)-) generation. H(2)O(2) induced apoptotic or necrotic cell death, depending on the concentration of the oxidant applied; low concentrations of H(2)O(2) preferentially activated the caspase-dependent apoptotic pathway, while high concentrations of H(2)O(2) induced apoptotic and necrotic cell death in a caspase-independent manner. The H(2)O(2)-induced cell death was associated with increased mitochondrial membrane potential collapse and caspase-3/7 activation and ER stress responses including...
Research Interests:
Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic (HC)... more
Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic (HC) IgEs can induce potent survival promotion, degranulation, cytokine production, migration, etc., whereas at the other end, poorly cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties. Enzyme-linked immunosorbent assays were performed to test whether IgEs bind antigens. Histamine-releasing factor in human sera was quantified by western blotting. Cultured mast cells derived from human cord blood were used to test the effects of human sera on cytokine production. Most (7/8) of mouse monoclonal HC IgEs exhibited polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), β-galacto...
Research Interests:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer treatment because of its selective cytotoxicity toward tumor cells. However, some cancer cell types including malignant melanoma cells are resistant... more
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer treatment because of its selective cytotoxicity toward tumor cells. However, some cancer cell types including malignant melanoma cells are resistant to TRAIL cytotoxicity. Here, we show that diallyl trisulfide (DATS), a garlic organosulfur compound, sensitizes melanoma cells to TRAIL-induced apoptosis while sparing normal cells. DATS also potentiates apoptosis induced by agonistic antibodies against death receptors (DR) 4 and DR5. The amplification of DR-mediated apoptosis was associated with increased mitochondrial membrane potential collapse and caspase-3/7 activation. However, these events were not sufficient for full sensitization. TRAIL also induced endoplasmic reticulum (ER) stress, as indicated by the activation of X-box-binding protein 1 and caspase-12 and DATS poten-tiated both events. Moreover, inhibition of caspase-12, but not caspase-4, abolished the amplification of apoptosis, indica...
Research Interests:
Research Interests:
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer treatment owing to its selective cytotoxicity against malignant cells. However, some cancer cell types, including malignant melanoma cells, are... more
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is promising for cancer treatment owing to its selective cytotoxicity against malignant cells. However, some cancer cell types, including malignant melanoma cells, are resistant to TRAIL-induced apoptosis. Therefore, drugs that can amplify TRAIL cytotoxicity are urgently required. Depolarization of the plasma membrane potential is associated with apoptosis induced by a variety of death-inducing agents but its role in apoptosis remains a matter of debate. We found that TRAIL treatment resulted in robust depolarization in human melanoma cells with a considerable lag (2-4 h). Moreover, membrane-depolarizing agents, including K+ and ATP-sensitive K+ (KATP) channel inhibitors glibenclamide and U37883A enhanced TRAIL-induced apoptosis. On the contrary, inhibitors of calcium- and voltage-dependent K+ channels and mitochondrial KATP channels had no such effects. Melanocytes were insensitive to TRAIL-induced depolarization and a...
Research Interests:
Mast cells play central roles in adaptive and innate immunity. IgE-dependent stimulation of the high-affinity IgE receptor (FcεRI) results in rapid secretion of various proinflammatory chemical mediators and cytokines. All of the outputs... more
Mast cells play central roles in adaptive and innate immunity. IgE-dependent stimulation of the high-affinity IgE receptor (FcεRI) results in rapid secretion of various proinflammatory chemical mediators and cytokines. All of the outputs depend to certain degrees on an increase in the intracellular Ca(2+) concentration, and influx of Ca(2+) from the extracellular space is often required for their full activation. There is strong evidence that FcεRI stimulation induces two different modes of Ca(2+) influx, store-operated Ca(2+) entry (SOCE) and non-SOCE, which are activated in response to endoplasmic reticulum Ca(2+) store depletion and independently of Ca(2+) store depletion, respectively, in mast cells. Although Ca(2+) release-activated Ca(2+) channels are the major route of SOCE, recent evidence indicates that they are not the only Ca(2+) channels activated by Ca(2+) store depletion. The recent data suggest that L-type Ca(2+) channels, which were thought to be a characteristic fea...
Research Interests:
IgE, a unique subclass of antibodies, leads to the development of allergic inflammation by eliciting mast cell activation. The molecular process of allergen specific IgE production which works for class switch recombination in B cells can... more
IgE, a unique subclass of antibodies, leads to the development of allergic inflammation by eliciting mast cell activation. The molecular process of allergen specific IgE production which works for class switch recombination in B cells can be a good target for the treatment of allergic disorders. Here, we review the mechanism of IgE class switch recombination in B cells, and then introduce current topics including our findings; (1) preferable usage of IgE VH families in subjects with allergic diseases; (2) allergic march and epitope spreading; and (3) regulation of IgE synthesis by cognate interaction between B cells and mast cells in the local inflammatory sites such as nasal mucosa and skin.
Research Interests:
Basophils are an active participant in the pathogenesis of local inflammation in allergic diseases such as asthma, but it is not fully known how basophil activation is regulated in inflamed tissue. In order to clarify the control... more
Basophils are an active participant in the pathogenesis of local inflammation in allergic diseases such as asthma, but it is not fully known how basophil activation is regulated in inflamed tissue. In order to clarify the control mechanisms of basophil activation in chronic inflammation and at remodeling sites, we analyzed the effects of fibroblast-derived cytokines, stem cell factor (SCF), and insulin-like growth factor-I (IGF-I) on basophils. The effects of SCF and IGF-I on degranulation and surface activation marker expression by basophils were assessed and compared. SCF enhanced human basophil histamine release elicited by some, but not all, secretagogues; degranulation in response to IgE- or FcepsilonRI-mediated stimulation and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) was enhanced by SCF. SCF slightly enhanced ionophore A23187-induced histamine release by basophils from some donors, but it failed to affect the release elicited by monocyte chemoattractant protein-1 (MCP-1), f...
Research Interests:
Reactive oxygen species (ROS), such as superoxide, hydrogen peroxide (H2O2), and hydroxyl radical, have for a long time been considered as accidental by-products of respiratory energy production in mitochondria and as being useless and... more
Reactive oxygen species (ROS), such as superoxide, hydrogen peroxide (H2O2), and hydroxyl radical, have for a long time been considered as accidental by-products of respiratory energy production in mitochondria and as being useless and rather deleterious to biological systems. Contrary to such a classical view, accumulating evidence indicates that upon stimulation of divergent receptor systems, ROS are intentionally produced and even required for appropriate signal transduction and biological responses. Work by our group and that of others have shown that stimulation of mast cells through the high-affinity IgE receptor (FcepsilonRI) induces the production of ROS such as superoxide and H2O2 possibly by the phagocyte NADPH oxidase homologue and that these endogenously produced oxidants have important functions in regulation of various mast cell responses, including degranulation, leukotriene secretion, and cytokine production. Subsequent studies have defined particular biochemical pat...
Research Interests:
Research Interests:
The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired... more
The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired corneal transparency when many corneal endothelial cells are lost due to various stresses. We determined whether Smad7, an intracellular antagonist of TGF-beta signaling, regulated the inhibitory activity of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation. The effect of Smad7 on TGF-beta2- or aqueous humor-mediated inhibition of corneal endothelial cell proliferation was evaluated using thymidine uptake assay with cultured rabbit corneal endothelial cells infected with adenovirus carrying Smad7. Expression of Smad or cell cycle-related proteins was detected by immunoblotting. In addition, a small scrape wound was made across a monolayer of Smad7-expressing cultured rabbit corneal endothelial cells to examine the effect of Smad7 o...