Involvement of apoptotic cell death in autoimmune diseases

Kawakami, Atsushi; Eguchi, Katsumi

doi:10.1007/s007950200000

Cited by 29 publications

(15 citation statements)

References 56 publications

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“…This active process involves cellular metabolism with gene activation and protein synthesis. It is assumed that the expression of apoptosis-related molecules is affected by numerous humoral and cellular factors [1]. Disorders in the regulation of programmed cell death that hinder elimination of cells reacting with their own antigen and thus promote their excessive proliferation constitute a major link in the development of many diseases, including autoimmune disorders of the thyroid [2].…”

Section: Introductionmentioning

confidence: 99%

Expression of Bcl-2 Family Proteins in Thyrocytes from Young Patients with Immune and Nonimmune Thyroid Diseases

Bossowski¹,

Czarnocka²,

Bardadin

et al. 2008

Horm Res Paediatr

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The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves’ disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.

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Section: Introductionmentioning

confidence: 99%

Expression of Bcl-2 Family Proteins in Thyrocytes from Young Patients with Immune and Nonimmune Thyroid Diseases

Bossowski¹,

Czarnocka²,

Bardadin

et al. 2008

Horm Res Paediatr

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show abstract

“…Our findings suggest that significant expression of TIAR may indicate on enhanced activity of egzogenous way of apoptosis in autoimmune diseases, for example in GD. Kawakami et al observed the association between the apoptosis of thyrocytes and the process of autoimmune thyroid diseases and suggested that Fas-mediated apoptosis of human thyrocytes is modulated by thyroid-stimulating antibodies, thyroid stimulation blocking antibodies and cytokines [20]. Similarly, we conclude that elevated expression of NIS and TPO in Graves' disease is associated with higher stimulation and activation of apoptosis in thyroid follicular cells during autoimmune process.…”

Section: Discussionmentioning

confidence: 67%

Identification of chosen apoptotic (TIAR and TIA-1) markers expression in thyroid tissues from adolescents with immune and non-immune thyroid diseases.

Bossowski

Czarnocka²,

Bardadin³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The aim of this study was to estimate sodium iodide symporter (NIS) and thyroid peroxidase (TPO) expression in thyrocytes from patients with GD and no-toxic multinodular goitre (NTMG) in relationship with apoptotic (TIAR and TIA-1) markers. The investigation was performed on thyroid cells isolated from postoperation thyroid tissues from 15 patients aged 12-21 years old with GD and 15 cases aged 13-21 years old with NTMG. Detection of NIS and TPO was performed by immunohistochemistry. Analysis of apoptotic markers in thyroid tissues was performed using antibodies to TIAR and TIA-1 by Western Blot and immunohistochemistry. Identification of proapoptotic TIAR and TIA-1 molecules in the thyroid tissues revealed a higher expression of both proteins in patients with Graves' disease (+++; +, respectively) in comparison to patients with NTNG (+; 0). In addition, TIAR expression was detected in three bands [p50, p42, p38 (kDa)] and TIA-1 in two bands [p22, p17 (kDa)]. using Western Blot test in patients with thyroid autoimmune diseases. In patients with NTNG expression of both apoptotic proteins was lower and identified in single bands: 42 (kDa) for TIAR and 17 (kDa) for TIA-1. The analysis of expression of NIS and TPO in thyroid follicular cells was higher in patients with Graves' disease in compared to their detection in patients with NTMG. In addition, degree of thyroid antigen expression positive correlated with amount of proapoptotic markers (TIAR, p<0.001; TIA-1, p<0.025 for NIS; TIAR, p<0.012 for TPO). We conclude that elevated expression of NIS and TPO in Graves' disease is associated with higher stimulation and activation of apoptosis in thyroid follicular cells during autoimmune process.

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“…This indicates that apart from CD64 expression, activation of target cells may be a prerequisite for the cytotoxic effect of CD64-RiA. Recent work indicates that insufficient apoptosis of inflammatory cells in RA joints might contribute to pathogenesis (27,28). Besides selective elimination, a strong inhibition of proinflammatory cytokines like TNF-␣ and IL-1␤ was observed (21).…”

Section: Discussionmentioning

confidence: 96%

CD64-Directed Immunotoxin Inhibits Arthritis in a Novel CD64 Transgenic Rat Model

Vuuren

Roon

Walraven

et al. 2006

The Journal of Immunology

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Macrophages are known to play a key role during inflammation in rheumatoid arthritis (RA). Inflammatory macrophages have increased expression of CD64, the high-affinity receptor for IgG. Targeting this receptor through a CD64-directed immunotoxin, composed of an Ab against CD64 and Ricin A, results in effective killing of inflammatory macrophages. In this study, we show elevated levels of CD64 on synovial macrophages in both synovial lining and synovial fluid in RA patients. The CD64-directed immunotoxin efficiently eliminates activated synovial macrophages in vitro, while leaving quiescent, low CD64-expressing macrophages unaffected. To examine whether killing of CD64 macrophages results in therapeutic effects in vivo, we established an adjuvant arthritis (AA) model in newly generated human CD64 (hCD64) transgenic rats. We demonstrate that hCD64 regulation in this transgenic rat model is similar as in humans. After AA induction, treatment with CD64-directed immunotoxin results in significant inhibition of disease activity. There is a direct correlation between immunotoxin treatment and decreased macrophage numbers, followed by diminished inflammation and bone erosion in paws of these hCD64 transgenic rats. These data support synovial macrophages to play a crucial role in joint inflammation in AA in rats and in human RA. Selective elimination of inflammatory macrophages through a CD64-directed immunotoxin may provide a novel approach for treatment of RA.

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Involvement of apoptotic cell death in autoimmune diseases

Cited by 29 publications

References 56 publications

Expression of Bcl-2 Family Proteins in Thyrocytes from Young Patients with Immune and Nonimmune Thyroid Diseases

Expression of Bcl-2 Family Proteins in Thyrocytes from Young Patients with Immune and Nonimmune Thyroid Diseases

Identification of chosen apoptotic (TIAR and TIA-1) markers expression in thyroid tissues from adolescents with immune and non-immune thyroid diseases.

CD64-Directed Immunotoxin Inhibits Arthritis in a Novel CD64 Transgenic Rat Model

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