Inhibition of fas antigen‐mediated apoptosis of rheumatoid synovial cells in vitro by transforming growth factor β1

Kawakami, Atsushi; Eguchi, Katsumi; Matsuoka, Naoki; Tsuboi, Masahiko; Kawabe, Yojiro; Aoyagi, Takahiko; Nagataki, Shigenobu

doi:10.1002/art.1780390802

Cited by 80 publications

(70 citation statements)

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“…However, little is known about the role of apoptosis in glandular destruction [9]. Recently, apoptotic cell death, especially Fasmediated apoptosis, has been reported to be involved in the development of other chronic inflammatory diseases such as RA [7] and UC [8]. Therefore, we examined both Fas/FasL and apoptotic cell death in the labial salivary glands from SS patients.…”

Section: Discussionmentioning

confidence: 99%

“…FasL protein was originally found in T cells [4], where diverse stimuli induced FasL gene expression [6,7], and it is believed that the expression of FasL is responsible for the killing activity of CD4 þ T cells and in part of CD8 þ T cells. The presence of apoptosis and the expression of Fas/FasL have been determined in the involved organs from human chronic inflammatory diseases such as the synovium from rheumatoid arthritis (RA) patients [7] and the colon from ulcerative colitis (UC) patients [8]. In addition, Kong et al have recently reported the expression of Fas/FasL in the salivary glands of patients with primary Sjögren's syndrome (pSS) [9].…”

Section: Introductionmentioning

confidence: 99%

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Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients

Nakamura

Koji

Tominaga

et al. 1998

Clinical and Experimental Immunology

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SUMMARYApoptosis is a type of cell death that occurs during morphogenesis and development of the immune system. One of the mechanisms is mediated through the Fas and Fas ligand (FasL) pathway. To determine the possible involvement of Fas and its ligand in salivary gland destruction, we analysed the appearance of nuclei with DNA fragmentation by using nick end labelling (TUNEL) and the expression of Fas and FasL by immunohistochemistry in labial salivary glands. Furthermore, we compared the features of apoptosis in labial salivary glands between HTLV-I ¹ and HTLV-I þ SS. When the frozen sections of 10 primary SS patients in the absence of anti-HTLV-I antibody were examined, several apoptotic cells were found in the acinar and ductal epithelial cells as well as infiltrated mononuclear cells. Both Fas and FasL were detected in the infiltrated mononuclear cells. Acinar epithelial cells, which are surrounded by FasL þ mononuclear cells, were also double-positive with Fas and FasL, although the expression of FasL was localized at their apical border, suggesting that apoptosis of mononuclear cells was achieved by activation-induced mechanisms through Fas/FasL pathways, and that of acinar epithelial cells was mediated by FasL derived from either acinar epithelial cells themselves or infiltrated mononuclear cells. Interestingly, Fas expression in ductal epithelial cells was localized around the lumen side of the ducts, indicating that FasL secreted from acinar epithelial cells may induce Fas-mediated apoptosis of ductal epithelial cells. We also studied the labial salivary glands from nine SS patients with anti-HTLV-I antibodies. There was no significant difference in the occurrence of apoptotic cells or in the expression of Fas and FasL between HTLV-I þ and HTLV-I ¹ SS patients. It was of note that neither the expression of Fas and FasL nor the presence of apoptotic cells were determined in labial salivary glands from subjects without SS. These findings indicate that Fasmediated apoptosis in salivary glands could be involved in the pathological manifestations of SS, irrespective of HTLV-I seropositivity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients

Nakamura

Koji

Tominaga

et al. 1998

Clinical and Experimental Immunology

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“…Following confirmation of the adequacy of permeabilization by trypan blue uptake, permeabilized cells were incubated with FITC-conjugated antiBcl-2 MoAb and examined by a flow cytometer. To check the adequacy of permeabilization on flow cytometric analysis, we used anti-a-tubulin MoAb (Cedarlane Labs, Ontario, Canada) as positive control antibody [7,18]. More than 99% of cells were positive with anti-a-tubulin MoAb.…”

Section: Flow Cytometric Analysis Of Fas and Bcl-2 On Thyrocytesmentioning

confidence: 99%

Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

Kawakami

Eguchi

Matsuoka

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe expression of two autoimmune thyroid diseases, GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-g) or IL-1b for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fasmediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1b or IFN-g caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1b or IFN-g was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1b or IFN-g, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1b or IFN-g. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1b or IFN-g. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.

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“…This peptide is a potent inducer of matrix protein synthesis. It is activated in a number of chronic inflammatory diseases, and it seems to mediate the perpetuation of synovial hyperplasia in RA patients (29). Diminution of TGFP expression could consequently be associated not only with matrix metabolism turnover, but also with the involution of pannus observed in chronic antigen-induced arthritis.…”

Section: Discussionmentioning

confidence: 99%

Antifibroproliferative effect of tenidap in chronic antigen‐induced arthritis

Sánchez‐Pernaute

López-Armada

Hernández

et al. 1997

Arthritis & Rheumatism

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Objective. To determine whether tenidap regulates extracellular matrix metabolism in chronic arthritis.Methods. Antigen arthritis was induced in the knees of 30 rabbits. Animals were distributed into 3 groups: untreated, tenidap-treated, and diclofenactreated rabbits. Three weeks after disease induction, synovial membranes were extracted and processed for histopathologic examination and detection of type I collagen (CI) and fibronectin (FN) by immunoperoxidase. Simultaneously, we analyzed the in vitro effect of tenidap on healthy synovial cell (SC) proliferation, FN expression and synthesis, and expression of transforming growth factor P l (TGFf31) messenger RNA.Results. Untreated animals showed synovial lining hyperplasia, cellular infiltration at the sublining, and increased deposition of matrix proteins. These findings were not apparent in tenidap-treated rabbits, where CI and FN had the same distribution as in healthy synovial membranes. In vitro, tenidap inhibited SC proliferation ( 2 2 5 pkf) and down-regulated the expression and synthesis of FN in a dose-dependent manner ( 1 1 a. This antifibrotic effect was associated with a reduction of TGFPl message.Conclusion. Tenidap down-regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease-modifying agent for rheumatoid arthritis.

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Inhibition of fas antigen‐mediated apoptosis of rheumatoid synovial cells in vitro by transforming growth factor β1

Cited by 80 publications

References 43 publications

Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients

Apoptosis in labial salivary glands from Sjögren's syndrome (SS) patients: comparison with human T lymphotropic virus-I (HTLV-I)-seronegative and -seropositive SS patients

Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

Antifibroproliferative effect of tenidap in chronic antigen‐induced arthritis

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