Molecular fingerprint of interferon-gamma signaling in unstable angina.
نویسندگان
چکیده
BACKGROUND Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-gamma. IFN-gamma induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-gamma driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10. METHODS AND RESULTS Peripheral blood mononuclear cells were stained for expression of CD64 on CD14(+) monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-gamma in vitro, with accelerated transcriptional competency of CD64. IP-10-specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients (P<0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-gamma signaling in vivo. CONCLUSIONS Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-gamma triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-gamma-inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-gamma. IFN-gamma may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.
منابع مشابه
Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T.
OBJECTIVE To measure plasma interferon gamma, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina. DESIGN Blood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease. PATIENTS 76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable a...
متن کاملPerturbation of the T-cell repertoire in patients with unstable angina.
BACKGROUND Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-gamma is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald's class IIIB) and with ...
متن کاملIncreased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation.
BACKGROUND There is growing evidence for a pathogenic role for cytokines in atherogenesis. The presence of certain cytokines has been documented in human atherosclerotic vessels. This study was designed to investigate cytokine production by mononuclear leukocytes from patients with ischemic heart disease. METHODS AND RESULTS We measured kinetics of secretion of tumor necrosis factor-alpha (TN...
متن کاملEvaluation of Salivary Interferon-Gamma Level in Patients with Recurrent Aphthous Stomatitis
Introduction: Recurrent aphthous stomatitis (RAS) is defined by recurring ulcers restricted to oral mucosa in the patients with no other signs of systemic disease. The purpose of this study was to evaluate the salivary level of interferon gamma in patients with RAS. Methods: In this case-control study, 30 patients with RAS (in Recurrence and recovery period) in the experimental and 25 healthy ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation
دوره 103 11 شماره
صفحات -
تاریخ انتشار 2001