Expression of Bcl‐2 in Inflammatory Sites from Patients with Active Behçet′s Disease

Abstract

Behçet's disease (BD) is a current systemic vasculitis of unknown aetiology. Eyes, skin, joints, the oral cavity, genital system, blood vessels, central nervous system and lung are usually involved. Defective regulation of programmed cell death (apoptosis) may play a role in the development of (BD), and the proto-oncogene Bcl-2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of Bcl-2 in the peripheral lymphocytes and in two inflammatory sites of patients with active BD: bronchoalveolar lavage (BAL) and cerebrospinal fluid (CSF) lymphocytes. Levels of Bcl-2 expression in the lymphocytes of patients with BD and, for comparison, in the lymphocytes of healthy controls and non-inflammatory neurological diseases (NIND), were studied by two-colour cytofluorography and RNA analysis. In BD patients, a significant proportion of T cells expressed increased amounts of Bcl-2 protein, both in peripheral blood and in inflammatory sites. Mononuclear cells of patients with BD showed increased amount of Bcl-2 messenger RNA. The in vitro incubation of T lymphocytes with IL-10, significantly increased the Bcl-2 expression, specifically in T lymphocytes from inflammatory sites. In active BD, stimulation of HSV-1 T lymphocytes slightly increased Bcl-2 expression, not significantly different from unstimulated HSV-1 T cells. The occurrence of circulating T lymphocytes with abnormally high Bcl-2 expression in peripheral circulation and in inflammatory sites may be explained in part by the increased in vivo activation levels, and by aetiopathological agent(s): our findings seem to indicate an important role in the chronic inflammation in BD.

Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behçet's disease

“…It was reported that peripheral lymphocytes from BD patients are resistant to Fas-induced apoptosis 23 24. In addition, the expression of anti-apoptotic protein Bcl-2 increased in the T lymphocytes in inflammatory sites of BD patients 25 26. The present study first discovered that GIMAP4 transcript levels in T lymphocytes of BD patients were significantly decreased when compared to their levels in healthy controls.…”

Changes in Exfoliative Cell of Oral Mucosa in Kidney Transplant Patients

“…Apoptotic cell density was increased in patients after kidney transplantation compared with before kidney transplantation. Similar to our results, lower apoptotic activity owing to immunosuppressive drug usage was reported in periphery lymphocytes and the oral epithelium [26,27]. Baris et al [28] found that both loss of transmembrane Fas-related signal and inhibition of apoptosis in the lymphocyte survival in Behçet's disease.…”

Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction

“…Other molecules are involved in the programmed cell death process, including members of the Bcl-2 gene family, which are known to inhibit apoptosis. Studies have shown that Bcl-2 expression is increased in lymphoid cells obtained from the airways of asthmatic patients and that neutralization of IL-10, an important inducer of Bcl-2, decreases Bcl-2 expression and apoptosis of cells from the respiratory tract of asthmatic patients (Hamzaoui et al 1999a;Hamzaoui et al 1999b). Because RAO in horses is a condition similar to human asthma, these apoptotic mechanisms might have an important role in the inflammatory processes described above.…”