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Y Kawabe

Publications and source records attributed to Y Kawabe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regulation of rheumatoid synovial cell growth by ceramide.

Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.

Apoptosis↗
PubMed2000

Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells.

Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.

Arthritis, Rheumatoid↗
PubMed2000

Prevalence of TTV DNA among children with a history of transfusion or liver disease.

The prevalence rates of serum TT virus (TTV) DNA among children with or without a history of transfusion or liver disease were studied by polymerase chain reaction (PCR) using either the Okamoto primer set or the Takahashi primer set developed more recently. Using Okamoto and Takahashi primer sets, the prevalence rates were 31.6% (12/38) and 78.9% (30/38), respectively, for children with a history of blood transfusion (including malignant and non-malignant groups) and 6.7% (2/30) and 60% (18/30), respectively, for children without a history of blood transfusion. Among pregnant women, these rates were 12.9% (4/31) and 61.3% (19/31), respectively. On the other hand, the prevalence rates were 0% (0/16) and 50% (8/16), respectively, in hepatitis B patients, 21.4% (3/14) and 71.4% (10/14), respectively, for hepatitis C patients, and 20.0% (9/45) and 57.8% (26/45), respectively, for non-A to C hepatitis patients (including 27 acute hepatitis patients, 5 fulminant patients and 13 chronic hepatitis patients). In this study, the prevalence rates determined by the Takahashi primer set tended to be 2-9 times higher than those determined using the Okamoto primer set. These results suggest that TTV infection is widespread among Japanese children. Furthermore, blood transfusion does not appear to be the major route of infection. The similar prevalence rates between control children and children with various types of hepatitis using the Takahashi primer system suggest that TTV infection does not play a direct causative role in the development of liver disease in children.

Adult↗
PubMed2000

Changes in the endocrine environment of the human prostate transition zone with aging: simultaneous quantitative analysis of prostatic sex steroids and comparison with human prostatic histological composition.

BACKGROUND: It is well-known that the incidence of benign prostatic hyperplasia (BPH) increases with aging. The age-dependent changes in the ratio of serum sex steroid concentrations may play a role in BPH development. To clarify the relationship between the prostatic tissue concentrations of these steroids and age, we established a precise method of simultaneous quantitative analysis for prostatic sex steroids and used this method to investigate the tissue concentrations of three major sex steroids (testosterone, dihydrotestosterone, and estradiol) in the human prostate. METHODS: The methodology for the simultaneous quantitative analysis of prostatic sex steroids was established using castrated rat prostatic tissue, coupled with internal standards, for androgen-deprived medium, and the validation of the method was examined. Human prostatic tissues were collected during surgery and immediately frozen at -70 degrees C. Using our method, the steroidal fractions were extracted, purified, and quantified. The proportions of stroma, epithelium, and glandular lumen were measured on each histological specimen, using an image analyzer. RESULTS: The validation tests showed that our method of quantitative analysis was precise and sensitive enough for the quantification of testosterone, dihydrotestosterone, and estradiol in the prostate. In humans, the prostatic dihydrotestosterone concentration decreased with age, but the concentrations of testosterone and estradiol showed no relation with age. Therefore, the ratio of estradiol to dihydrotestosterone concentration (E2/DHT) in prostate increased with age. The E2/DHT ratio showed a significant positive correlation with the proportion of stroma. CONCLUSIONS: The age-dependent decrease in prostatic dihydrotestosterone and constant estradiol concentration lead to a relatively estrogen-dominant environment compared to that at younger ages. We assume that this relatively estrogen-dominant status induces stromal proliferation by some mechanism and leads to the development of BPH.

Aged↗
PubMed2000

Carbohydrate metabolism during starvation in the silkworm Bombyx mori.

The effect of starvation on carbohydrate metabolism in the last instar larvae of the silkworm Bombyx mori was examined. Trehalose concentration in the hemolymph increased slightly during the first 6 h of starvation and decreased thereafter, whereas glucose concentration decreased rapidly immediately after diet deprivation. Starvation-induced hypertrehalosemia was completely inhibited by neck ligation, suggesting that starvation stimulates the release of a hypertrehalosemic factor(s) from the head. The percentage of active glycogen phosphorylase in the fat body increased within 3 h of starvation and its glycogen content decreased gradually. These observations suggest that production of trehalose from glycogen is enhanced in starved larvae. However, hypertrehalosemia during starvation cannot be explained by the increased supply of trehalose into hemolymph alone, as similar changes in phosphorylase activity and glycogen content in the fat body were observed in neck-ligated larvae, in which hemolymph trehalose concentration did not increase but decreased gradually. When injected into larvae, trehalose disappeared from hemolymph at a rate about 40% lower in starved larvae than neck-ligated larvae. The hemolymph lipid concentration increased during starvation, suggesting that an increased supply of lipids to tissues suppresses the consumption of hemolymph trehalose and this is an important factor in hypertrehalosemia.

Animals↗
PubMed2000

FK506 augments glucocorticoid-mediated cyclooxygenase-2 down-regulation in human rheumatoid synovial fibroblasts.

Prostaglandins (PG) formed by cyclooxygenase (COX) enzymes are important mediators of inflammation in rheumatoid arthritis. The contribution of the inducible COX-2 to inflammation in the rheumatoid synovium is well documented. We examined the regulation of COX-2 mRNA and protein expression in response to both glucocorticoids (GC) and FK506 using rheumatoid synovial fibroblasts. Combined treatment of FK506 and a low concentration of dexamethasone (DEX) (10(-9) M) down-regulated synovial COX-2 mRNA and protein expression. In contrast, neither FK506 nor DEX (10(-9) M) alone influenced COX-2 expression. Immunocytochemical studies showed that pretreatment with FK506 enhanced the nuclear translocation of the glucocorticoid receptor (GR) in synovial fibroblasts in the presence of low concentrations of DEX (10(-9) M). Transient transfection experiments showed that treatment of cells with FK506 enhanced the expression of glucocorticoid-responsive gene reporter in the presence of DEX (10(-9) M). NF-kappaB is known to mediate the transcriptional activation of the COX-2 gene. Electrophoretic mobility shift assay demonstrated that DNA-binding activity of NF-KB was suppressed more profoundly by FK506 plus DEX (10(-9) M) treatment with those of DEX (10(-9)M) alone in IL-1beta-stimulated synovial cells. Our results indicated that FK506-induced potentiation of GR-mediated repression of synovial COX-2 gene transcription is the result of increased translocation of GR to the nucleus and subsequent repression of NF-kappaB transactivation. Our results also suggest that FK506 may exert anti-inflammatory effects in the rheumatoid synovium by potentiating GR-mediated signal transduction.

Arthritis, Rheumatoid↗
PubMed2000

CD4+ T cell-mediated cytotoxicity toward thyrocytes: the importance of Fas/Fas ligand interaction inducing apoptosis of thyrocytes and the inhibitory effect of thyroid-stimulating hormone.

The accumulation of activated CD4+ T cells and antigen (Ag)-dependent cellular interactions between thyrocytes and CD4+ T cells have been determined in thyroid gland from patients with Graves' disease. The Fas/Fas ligand (FasL) interaction between antigen-presenting cells and T cells regulates the apoptosis of the former cells triggered by the latter cells. The inhibition of Fas-mediated apoptosis in thyrocytes could be a underlying mechanism of hyperplasia of thyrocytes in patients with Graves' disease. We investigated the potential role of Fas/FasL interaction between thyrocytes and CD4+ T cells in the induction of Fas-mediated apoptosis of the former cells induced by the latter cells. The presence of only a few specific T cells responsive to a putative autoantigen has hampered the investigation of specific T cell activation toward antigen-presenting cells (APCs). Therefore, we used a superantigen, staphylococcal enterotoxin B (SEB), to examine specific T cell activation toward thyrocytes in vitro since it stimulates a large proportion of T cells with particular Vbeta elements. Spontaneous apoptosis of thyrocytes in culture was not found even in the presence of various kinds of cytokines. In contrast, a clear induction of Fas-mediated apoptosis by anti-Fas IgM was determined in interferon-gamma (IFN-gamma)-stimulated thyrocytes. In addition, a significant cytotoxicity of purified CD4+ T cells toward IFN-gamma-stimulated thyrocytes in the presence of SEB was induced, and the addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or blockade of the Fas/FasL interaction reduced this cytotoxicity. FasL expression of CD4+ T cells cocultured with IFN-gamma-stimulated thyrocytes in the presence of SEB was clearly induced. Furthermore, the addition of mAbs against CD54 and CD58 inhibited both cytotoxicity and FasL expression of CD4+ T cells. The cytotoxicity of CD4+ T cells toward IFN-gamma-stimulated, SEB-pulsed thyrocytes was markedly inhibited when we used thyrocytes cultured with IFN-gamma in the presence of thyroid-stimulating hormone (TSH) as target cells. Our results suggest that 1) CD4+ T cells were activated by thyrocytes expressing MHC class II molecules in an SEB-dependent manner and then expressed FasL. 2) These activated FasL+ CD4+ T cells killed thyrocytes by interacting with Fas on thyrocytes and FasL on activated CD4+ T cells. The presence of costimulating molecules such as CD54 and CD58 on thyrocytes was also necessary to generate activated FasL+ CD4+ T cells. 3) Since the actions of thyroid stimulating antibody (TSAb) toward thyrocytes are similar to those of TSH, one goitrogenic activity of TSAb may, in part, be due to the inhibitory effect on Fas-mediated apoptosis of thyrocytes triggered by activated CD4+ T cells.

Apoptosis↗
PubMed2000

Expression and function of X chromosome-linked inhibitor of apoptosis protein in Sjögren's syndrome.

Apoptotic cell death in acinar and ductal epithelial cells is thought to play an important role in the development of salivary gland dysfunction in patients with Sjogren's syndrome (SS). We examined the expression of anti-apoptotic molecules in salivary glands from patients with SS. The labial salivary glands from six human T-cell leukemia virus (HTLV)-I-seronegative and eleven HTLV-I-seropositive SS patients were analyzed by immunohistochemistry. In vitro experiments were performed with a human salivary gland cell line (HSG cells). Immunohistologic analyses revealed that Bcl-2 and Bcl-x were preferentially expressed in salivary infiltrating mononuclear cells more than acinar and ductal epithelial cells. In contrast, strong X chromosome-linked inhibitor of apoptosis protein (XIAP) expression was evident in both acinar and ductal epithelial cells. The pattern of expression of these anti-apoptotic molecules was similar in both HTLV-I-seropositive and HTLV-I -seronegative SS patients. Western blot analysis confirmed expression of XIAP in cultured HSG cells. The expression of XIAP in HSG cells was increased by IL-1beta, TGF-beta1, or IL-10. However, XIAP expression was down-regulated by TNF-alpha, which induced apoptotic cell death of HSG cells with an increase in caspase-3 activity. These effects of TNF-alpha in HSG cells were antagonized by IL-1beta, TGF-beta1, or IL-10. Our results suggest that XIAP is important in regulating apoptotic cell death of acinar and ductal epithelial cells in patients with SS.

Adult↗
PubMed2000

Expression of cyclooxygenase-1 (COX-1) in labial salivary glands of Sjögren's syndrome.

COX plays an important role in inflammatory diseases such as rheumatoid arthritis. To determine the role of COX in Sjögren's syndrome (SS), we examined COX expression in the salivary glands of SS patients. We examined 15 patients with SS and two normal subjects. Labial salivary gland tissue samples were analysed immunohistochemically using anti-COX-1 and COX-2 antibodies. All biopsy samples from 15 patients with SS were stained for COX-1. In contrast, COX-1 immunostaining was not detected in normal salivary gland tissues. Co-expression of COX-1 and CD68 was confirmed by mirror section technique and double antibody immunostaining. This finding indicated that COX-1-expressing cells in SS salivary glands were infiltrating macrophages. In contrast to COX-1 staining, only a little COX-2 immunostaining was observed in salivary gland tissues from SS patients. These data suggest that COX-1 expression on infiltrating macrophages may contribute to the inflammatory process of salivary glands in SS.

Adult↗
PubMed2000

Nuclear factor-kappaB and caspases co-operatively regulate the activation and apoptosis of human macrophages.

Accumulating evidence suggests that macrophages function as major effector cells in the pathological process of various human diseases. We examined here the role of nuclear factor-kappaB (NF-kappaB) and caspases in the regulation of activation and apoptosis of macrophages. Activation of the human monoblastic leukaemia cell line, U937, by phorbol 12-myristate 13-acetate (PMA) increased the expression of CD14/CD86, and cytokine production. PMA stimulation also increased the expression of both pro-caspase-8 and pro-caspase-3 in U937, but not apoptosis or intracellular caspase-3 activity. PMA also increased the expression of X-chromosome-linked inhibitor of apoptosis protein (XIAP) in U937, suggesting an inhibitory action for XIAP on the caspase cascade in PMA-stimulated U937. Electrophoretic mobility shift assay (EMSA) showed a significant increase of nuclear NF-kappaB activity in PMA-stimulated U937. When a potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was added to U937 cell culture in the presence of PMA, apoptosis was triggered by activation of caspase-3, which was induced by caspase-8 activation. XIAP expression was markedly suppressed in PMA-treated U937 in the presence of PDTC. The inhibitors of caspase-8 and caspase-3 mostly inhibited apoptosis of U937 treated with PMA in the presence of PDTC. Furthermore, a phenotype of U937 treated with PMA and PDTC in the presence of caspase inhibitor was almost identical to that of unstimulated U937. Our results suggest that the signalling pathways involved in the activation and apoptosis of human macrophages could be co-operatively regulated by the use of NF-kappaB and caspase inhibitors, thus enabling the control of macrophage function and number.

Apoptosis↗
PubMed2000

Relationship between Sjögren's syndrome and human T-lymphotropic virus type I infection: follow-up study of 83 patients.

We have previously demonstrated a high prevalence of Sjögren's syndrome (SS) in patients with human T-lymphotropic virus type I-associated myelopathy (HAM) in Nagasaki prefecture. The present follow-up study compared the clinical and laboratory findings of SS with or without human T-lymphotropic virus type I (HTLV-I) antibody in this endemic area for HTLV-I infection. We investigated the clinical and laboratory manifestations in 83 patients with SS and HAM, including histologic examination of labial salivary glands and the prevalence of SS in patients with HAM. Definite SS was diagnosed in 13 out of 20 patients with HAM when the European Community criteria were used. The density of mononuclear cell infiltration in labial salivary glands was higher in HTLV-I-seropositive patients with SS (including patients with HAM) than in HTLV-I-seronegative patients. The volume of saliva and lacrima determined by the Schirmer or Saxon test was lower than normal but was not different among SS-HTLV-I-seronegative patients, HTLV-I-seropositive patients without HAM, and HTLV-I-seropositive patients with HAM. The proportions of patients positive for antinuclear antibody (ANA) and anti-SS-A (Ro) antibody or anti-SS-B (La) antibody were similar in the three groups. However, the low volume of saliva and the frequency of ANA in SS correlated with the degree of mononuclear cell infiltration in labial salivary glands. Our results suggested that HTLV-I infection is related to SS and that laboratory and clinical findings in SS closely correlate with the degree of mononuclear cell infiltration in the salivary glands.

Adult↗
PubMed2000

Effect of vitamin K2 on osteoblast apoptosis: vitamin K2 inhibits apoptotic cell death of human osteoblasts induced by Fas, proteasome inhibitor, etoposide, and staurosporine.

Vitamin K2 is used for the treatment of osteoporosis, but the precise mode of action is still not clear. We investigated the effects of vitamin K2 on apoptosis of human osteoblasts. Human osteoblastic cell line MG63 cells and human primary osteoblast-like cells obtained from bone fragments in corrective surgery were used as human osteoblasts. Cells were cultured with or without various concentrations of vitamin K2 and tumor necrosis factor-alpha (TNF-alpha). We then determined the proliferative response, expression of Fas and Bcl-2-related proteins, and Fas-mediated apoptosis of these cells induced by anti-Fas immunoglobulin M (IgM). In addition, the effect of vitamin K2 in osteoblast apoptosis induced by Z-Leu-Leu-Leu-aldehyde (LLL-CHO), etoposide, or staurosporine was also examined. Human osteoblasts did not show spontaneous apoptosis in culture, even in the presence of vitamin K2 or TNF-alpha. Furthermore, proliferation of the cells was not influenced by vitamin K2 or TNF-alpha. Fas was functionally expressed on human osteoblasts, and the treatment with TNF-alpha significantly enhanced both Fas expression and Fas-mediated apoptosis of osteoblasts. The addition of vitamin K2 to the culture resulted in a dose-dependent inhibition of functional Fas expression on osteoblasts, in the presence or absence of TNF-alpha. Treatment of human osteoblasts with vitamin K2 clearly suppressed Bax expression of the cells, although the expression of Bcl-2 was not influenced by vitamin K2. Fas ligand (FasL) cDNA transformants were cytotoxic against osteoblasts, and the cytotoxicity was increased when osteoblasts were treated with TNF-alpha. The addition of vitamin K2 to osteoblasts significantly decreased the cytotoxic effects of FasL cDNA transformants. Furthermore, apoptosis of human osteoblasts induced by LLL-CHO, etoposide, or staurosporine was also clearly suppressed in vitamin K2-treated osteoblasts. Our results suggest that vitamin K2 inhibits apoptotic cell death of osteoblasts and maintains the number of osteoblasts. These actions may explain the therapeutic efficacy of vitamin K2 in osteoporosis.

Apoptosis↗
PubMed2000

Regulation of cyclooxygenase-2 expression in human osteoblastic cells by N-acetylcysteine.

Cyclooxygenase (COX) plays a pivotal role in the inflammatory process of inflammatory arthropathies. Inflammatory cytokines induce COX-2 expression in osteoblasts of inflamed joints, followed by osteoclast activation. The inhibition of COX-2 expression could help prevent prostaglandin E2 secretion, followed by osteoclast activation for bone destruction and resorption. We examined whether the antioxidant N-acetylcysteine (NAC) inhibited COX-2 expression induced in the human osteoblastic cell line MG63 by interleukin-1beta (IL-1beta). According to Western blot and reverse transcription-polymerase chain reaction (RT-PCR) test results, NAC inhibited IL-1beta-induced COX-2 expression in protein and messenger RNA. We also demonstrated immunohistochemically that NAC inhibited NFkappaB nuclear translocation. These results suggested that NAC inhibited both COX-2 expression and NFkappaB nuclear translocation in MG63, which in turn indicated that NAC could inhibit the inflammatory process involved in bone resorption by regulating COX-2 expression at the level of transcription.

Acetylcysteine↗
PubMed2000

Successful combined therapy of cyclophosphamide and cyclosporine for acute exacerbated interstitial pneumonia associated with dermatomyositis.

Interstitial pneumonia of polymyositis and dermatomyositis (PM/DM), especially the rapid progressive type, is a serious complication. We report a case of acute exacerbated interstitial pneumonia associated with DM. The respiratory distress condition was refractory to steroid pulse therapy and cyclosporine, however, there was a good response to additional intravenous cyclophosphamide pulse therapy (IVCY). We propose the possibility that the combination of these immunosuppressants might be useful for interstitial pneumonia with DM which is resistant to conventional steroid therapies.

Acute Disease↗
PubMed2000

MR imaging of the salivary glands in sicca syndrome: comparison of lipid profiles and imaging in patients with hyperlipidemia and patients with Sjögren's syndrome.

OBJECTIVE: We correlated abnormalities on MR imaging with the plasma lipid profiles of patients with hyperlipidemia and symptoms of sicca syndrome. SUBJECTS AND METHODS: MR imaging features of the salivary glands, salivary function, immunologic abnormalities, and plasma lipid profiles were analyzed in 24 patients with hyperlipidemia and symptoms of sicca syndrome and compared with those of 50 patients with Sjögren's syndrome. RESULTS: Swelling of the parotid gland, impaired salivary flow, or both were observed in 20 (83%) of 24 patients with hyperlipidemia and symptoms of sicca syndrome. MR imaging findings included an enlarged parotid gland replaced with extensive lipid infiltration, whereas sialography of the parotid gland revealed normal findings. Immunologic studies and analyses of the labial glands of the mouth revealed distinctive features in patients with Sjögren's syndrome. Importantly, elevated levels of plasma triglyceride correlated with parotid gland swelling, and increased cholesterol levels significantly affected salivary flow. CONCLUSION: Our findings suggest a distinct entity of sicca syndrome in patients with hyperlipidemia compared with patients with Sjögren's syndrome. Characteristic MR imaging findings of salivary glands in patients with hyperlipidemia included extensive lipid infiltration and gland enlargement.

Adolescent↗
PubMed2000

[Acute respiratory failure caused by tuberculosis requiring mechanical ventilation].

The patients with active tuberculosis in whom respiratory failure requiring mechanical ventilation developed were studied retrospectively. Nine patients (M 8, F 1) were identified at the National Tokyo Hospital during 5 years from January, 1993 to December, 1997. Seven of 9 patients were single men, and the duration of symptoms before admission was over 1 month in all patients, while the time from first visit to diagnosis was less than 7 days. All patients were identified as malnourished, and 7 patients suffered from another underlying diseases. The patients were classified into two groups. Six of 9 patients had pulmonary tuberculosis and the other three had miliary disease. The proportion of cases requiring mechanical ventilation was 0.3% and 8.6%, respectively, in pulmonary tuberculosis and miliary tuberculosis. At the start of mechanical ventilation, PaO2/FIO2 was lower than 200 in all 9 patients, and 6 patients were probably ARDS. Steroids (methylprednisolone 250-1000 mg/day) were used in all 9 patients. Despite the use of mechanical ventilation and antituberculous therapy, 8 out of 9 patients died. Only one patient with miliary tuberculosis survived. The establishment of the therapy for acute respiratory failure is needed so as to improve prognosis of such cases. At the same time, the delay in consulting a doctor led to acute respiratory failure in most cases, so it is also important to encourage tuberculosis patients to visit a doctor as soon as possible, after the appearance of symptoms.

Acute Disease↗
PubMed1999

Inhibition of caspase cascade by HTLV-I tax through induction of NF-kappaB nuclear translocation.

NF-kappaB is required for prevention of apoptosis. We examined the importance of human T-cell leukemia virus-I (HTLV-I) Tax protein to stimulate NF-kappaB nuclear translocation, thus preventing apoptosis. Jurkat cells and JPX-9 cells in which the inducible Tax expression plasmid vector was stably transfected were used in the present study. Both Jurkat and Tax(-) JPX-9 cells had small amounts of basal nuclear NF-kappaB activity. The addition of NF-kappaB inhibitors suppressed NF-kappaB nuclear translocation of the cells, thus inducing apoptosis. Sequential activation of caspases from caspase-8 to caspase-3 was shown during this process. NF-kappaB nuclear translocation in JPX-9 cells was stimulated through Tax expression, and both the activation of caspases and apoptosis induced by NF-kappaB inhibitors were significantly suppressed in the Tax(+) JPX-9 cells. The expression of Bcl-2, Bax, and Bcl-x was not changed among Jurkat, Tax(-) JPX-9, and Tax(+) JPX-9 cells in the presence or absence of NF-kappaB inhibitors. X-chromosome-linked inhibitor of apoptosis (XIAP) protein expression in Tax(-) JPX-9 cells was significantly suppressed by NF-kappaB inhibitors, however, its expression in Tax(+) JPX-9 cells was maintained even by the addition of NF-kappaB inhibitors. Our results suggest that the activation of NF-kappaB via Tax protein in HTLV-I infected cells renders the cells resistant to apoptosis. The expression of anti-apoptotic gene products such as XIAP to suppress caspase cascade, results in an increase of cytokine production and cell proliferation; one of the proposed mechanisms that promotes autoimmune disorders such as Sjögren's syndrome and rheumatoid arthritis found in HTLV-I seropositive subjects.

Apoptosis↗