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I Katayama

Publications and source records attributed to I Katayama.

400 records · Page 23Linked to original sources

Nitrite production in mouse 3T3 fibroblasts by bleomycin-stimulated peripheral blood mononuclear cell factors.

OBJECTIVE: It is well known that bleomycin induces tissue fibrosis, including pulmonary fibrosis or scleroderma-like conditions. However, the pathogenesis has not been completely elucidated. We recently observed that peripheral blood mononuclear cells (PBMCs) stimulated by bleomycin show growth stimulatory activity for fibroblasts. Nitric oxide (NO) is an important mediator of immune and inflammatory responses, and has recently been suggested to play a role in the pathogenesis of autoimmune disorders. In this study, we have examined whether bleomycin-stimulated PBMCs induce nitrite production in mouse 3T3 fibroblasts in vitro. METHODS: PBMCs were obtained from 6 patients with systemic sclerosis (SSc) and 6 normal volunteers, and stimulated by bleomycin; the culture supernatants were collected as conditioned medium (CM). The release of nitrite from 3T3 fibroblasts after incubation with CM was determined by Griess reagents. Induction of inducible NO synthase (iNOS) mRNA expression in 3T3 fibroblasts after incubation with CM was examined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. RESULTS: Bleomycin induced significant nitrite release from PBMCs in a time-dependent manner. Stimulation with CM increased nitrite production in 3T3 fibroblasts, which was significantly inhibited by antibodies against interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and iNOS inhibitor, L-NMMA. CM from SSc patients induced higher amounts of nitrite from 3T3 fibroblasts, compared with that from normal subjects, although the difference was not significant. CM induced iNOS mRNA expression in 3T3 fibroblasts in a time-dependent manner. CONCLUSION: These results suggest that bleomycin, as well as IL-1 beta and TNF-alpha, induce NO release from mononuclear cells, and that these cytokines furthermore stimulate fibroblasts to produce NO, which raises the possibility of the involvement of NO in the development of tissue fibrosis induced by bleomycin.

3T3 Cells↗

Clinical analysis of staphylococcal superantigen hyper-reactive patients with psoriasis vulgaris.

It has been recently hypothesized that superantigens, which stimulate T cells expressing particular T cell receptor Vbeta chain gene segments, play a precipitating or aggravating role in psoriasis. In this study, we investigated the peripheral blood mononuclear cell (PBMC) response of patients with psoriasis vulgaris to staphylococcal superantigens (staphylococcal enterotoxin A (SEA), SEB, and SEC1) and its relationship to clinical and laboratory findings. Cytokine secretion was assessed by ELISA in the supernatants of the cultured PBMCs stimulated with SEB. Results of 3H-TdR uptake showed that the PBMCs' response against SEB in patients with psoriasis vulgaris (34,468 +/- 6,455) (mean DPM SD) was significantly higher than that of normal subjects (22,756 +/- 5,780) (p < 0.005). The stimulation index (SI) of patients with psoriasis vulgaris (n = 37) (63.9 +/- 55) was significantly higher than that of normal subjects (n = 24) (26.0 +/- 23) (p < 0.005) and patients with atopic dermatitis (n = 10) (40.7 +/- 30) (p < 0.05). Similar results were obtained in response to SEA and SEC1. SI weakly correlated with the psoriasis area and severity index (PASI) score (r = 0.62) and the serum interleukin-6 (IL-6) concentration (r = 0.45). IL-2 and tumor necrosis factor (TNF-alpha) were secreted at a significantly increased level by PBMCs from psoriatic patients on incubation with SEB, after a 3 day culture period. A higher level of IL-6 was released by PBMCs stimulated with SEB in psoriatic patients than normal controls, however, the difference was not significant. These results raise the possibility that monocytes, as well as T cells, are markedly activated by staphylococcal superantigen in patients with psoriasis vulgaris, which may play a role in the triggering or aggravating of psoriasis mediated by secreted cytokines.

Case-Control Studies↗

Peripheral blood mononuclear cell proliferative response against staphylococcal superantigens in patients with psoriasis arthropathy.

It has been recently hypothesized that superantigens play a precipitating or aggravating role in psoriasis. Aside from streptococcal infection, Staphylococcus aureus can be sometimes detected in the tonsils of patients with psoriasis arthropathy (PA), although its significance in the pathogenesis of PA is still unknown. These focal infections are thought to be a possible triggering factor of the arthralgia, as well as the cutaneous manifestations, in PA. In this study, we have investigated the response of peripheral blood mononuclear cells (PBMC) from patients with PA to staphylococcal superantigens and analyzed its association with clinical and laboratory findings. 3H-TdR uptake by PBMC was examined after 7 days' culture with concanavalin A (Con A), staphylococcal enterotoxin A (SEA), SEB and SEC1. Results showed that there was no significant difference in either the unstimulated or Con A-stimulated PBMC response between psoriasis vulgaris patients (PASI score < 10) (n = 15), PA patients (n = 11) and normal controls (n = 19). Among 11 PA patients, 8 patients responded most intensely to SEB, while 2 patients showed the strongest response to SEA, and another responded mainly to SEC1. The PBMC response against SEB in patients with PA (38,715 719 dpm, stimulation index (SI); 50.2 41.4) (mean SD) was significantly higher than that in normal controls (23,708 466 dpm, SI; 30.9 23.8) (p < 0.05), however, the difference between that of patients with PA and psoriasis vulgaris (33,428 467 dpm, SI; 42.8 30.6) did not reach significance. In addition, PBMC from psoriatic patients with a short episode of severe, disabling lumbago, which occured following sudden onset throat soreness, showed a stronger response against SEB (SI; 73.7 39.7), as compared with that of PA patients without such an episode (SI; 42.6 18.1). However this difference did not reach significance. Several immune abnormalities, including positive antinuclear antibodies or rheumatoid factor were observed mainly in the group experiencing such an episode of severe lumbago. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that predominant expression of the T cell receptor (TCR) Vbeta 17 was commonly detected in both synovial tissues and paired peripheral bloods in two cases examined. In one case, Vbeta 12 was preferentially expressed, and in another case, Vbeta 10, 15 and 19 were also strongly expressed in the infiltrating lymphocytes in the synovial tissues. Our data raised the possibility that staphylococcal superantigens may also play an exacerbating role in PA.

Adult↗