Increased TNF-alpha and decreased TGF-beta expression in peripheral blood leukocytes after acute myocardial infarction.
ABSTRACT Inflammation contributes to the development of atherosclerosis and cardiovascular events. Counteracting pro- and anti-inflammatory responses of serum cytokines have been reported, but the relevance of TNF-alpha, TGF-beta and IL-6 gene expression in peripheral blood leukocytes and their contribution to systemic inflammation in atherosclerosis, especially after acute myocardial infarction (AMI), has not been investigated yet. Using quantitative RT-PCR, we determined temporal cytokine mRNA expression alterations in blood cells from patients with AMI (n = 51). Serum cytokine concentrations were analyzed in parallel using the ELISA technique. TNF-alpha mRNA expression rates and serum concentrations were significantly elevated in AMI patients compared to controls (n = 77), while mRNA expression and serum content of TGF-beta were decreased. Interestingly, we found no statistically significant correlation between transcript and protein levels, indicating that gene expression in leukocytes may be an independent sign for systemic inflammation. While IL-6 was significantly increased in serum from AMI patients with positive correlation to left ventricular dysfunction and negative correlation to ejection fraction, IL-6 mRNA levels did not differ between patients and controls. Gene expression alterations indicate a sophisticated regulation of counteracting TNF-alpha and TGF-beta cytokine expression in peripheral blood leukocytes after AMI with bias towards a pro-inflammatory situation.
Article: Changes in transforming growth factor β and its receptors' mRNA expression in monocytes from patients with acute coronary syndromes.[show abstract] [hide abstract]
ABSTRACT: Transforming growth factor β (TGF-β) is thought to be a vasoprotective cytokine. Numerous reports confirm its significance in blood and plaques. There is, however, a lack of information on the molecular mechanisms involving TGF-β in circulating inflammatory cells in atherogenesis. sThe aim of the study was to assess gene expression of TGF-β and its receptors in monocytes from patients with acute coronary syndromes (ACS) and the effect of standard treatment on the studied genes. The study was carried out in 32 patients with ACS and 15 healthy subjects. Gene expression of TGF-β and receptors TGF-βRI and TGF-βRII was evaluated on day 1 and 5 in the study group and once in controls. The number of mRNA copies isolated from monocytes was assessed by QRT-PCR. Monocytes of ACS patients showed slightly elevated transcriptional activity of TGF-β1 and its receptors RI and RII genes (0.29 ±0.043 vs. 0.08 ±0.020, p = 0.05; 0.071 ±0.022 vs. 0.036 ±0.023, p < 0.05; 0.134 ±0.020 vs. 0.048 ±0.016, p < 0.05, respectively). After 5-day standard treatment modest reduction of TGF-βRI expression was observed. The studied genes' expression was unrelated to ejection fraction, myocardial necrosis markers, GRACE score, time from the onset of pain to percutaneous coronary intervention and angiographic findings. Among risk factors family history of CAD was associated with increased TGF-βRI expression. Moreover, the presence of 4 or more classic risk factors correlated with higher TGF-βRI expression. Monocytes of ACS patients demonstrate overexpression of TGF-β1 and its receptors' genes. Five-day standard treatment downregulated the TGF-βRI gene but did not affect TGF-β1 and TGF-βRII.Archives of medical science : AMS. 08/2010; 6(4):526-32.
Article: One-Year Supplementation with a Grape Extract Containing Resveratrol Modulates Inflammatory-Related microRNAs and Cytokines Expression in Peripheral Blood Mononuclear Cells of Type 2 Diabetes and Hypertensive Patients with Coronary Artery Disease.[show abstract] [hide abstract]
ABSTRACT: Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbAlc or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect that may contribute to treatment.Pharmacological Research 04/2013; · 4.44 Impact Factor
Article: MIG and the regulatory cytokines IL-10 and TGF-β1 correlate with malaria vaccine immunogenicity and efficacy.[show abstract] [hide abstract]
ABSTRACT: Malaria remains one of the world's greatest killers and a vaccine is urgently required. There are no established correlates of protection against malaria either for natural immunity to the disease or for immunity conferred by candidate malaria vaccines. The RTS,S/AS02A vaccine offers significant partial efficacy against malaria.mRNA expression of five key cytokines interferon-gamma (IFN-γ), monokine induced by gamma (MIG), interleukin-10 (IL-10), transforming growth factor-β (TGF-β) and forkhead box P3 (FoxP3) in peripheral blood mononuclear cells were measured by real-time RT-PCR before and after vaccination with RTS,S/AS02A and Modified Vaccinia virus Ankara encoding the circumsporozoite protein (MVA-CS) in healthy malaria-naïve adult volunteers. The only significant change was in IFN-γ mRNA expression, which was increased seven days after vaccination (P = 0.04). Expression of MIG mRNA seven days after vaccination correlated inversely with time to detection of parasites by blood film in an experimental sporozoite challenge (r = 0.94 P = 0.005). An inverse relationship was seen between both TGF-β1 and IL-10 mRNA at baseline and the anti-circumsporozoite IgG antibody response (r = -0.644 P = 0.022 and r = -0.554 P = 0.031 respectively). This study demonstrates the potential for MIG expression as a correlate of protection against malaria. Baseline levels of the regulatory cytokines TGF-β and IL-10 inversely correlated with antibody levels post vaccination and warrant further studies to improve understanding of individual differences in response to vaccination.PLoS ONE 01/2010; 5(9):e12557. · 4.09 Impact Factor