Flowchart: Preparation: Cd25








Text Box:   Il2



Rheumnatic disease



Text Box:  CD25





Int Immunopharmacol. 2006 Jun;6(6):1034-8. Epub 2006 Feb 3.

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IL-2 increased RANTES production and CD25 expression in cultured PBMCs only from antiretroviral treated HIV-1+ patients with detectable viral loads.

Lozano JM, Kindelan JM, Cabello A, Gonzalez R, Solana R, Pena J.

Department of Immunology, Hospital "Reina Sofia", University of Cordoba, Spain; Department of Virology, Pasteur Institute of Paris, France.

In order to better understand the possible beneficial effects of intermittent IL-2 treatment as complement of antiretroviral therapy in HIV-1+ patients, we have measured the levels of RANTES in the supernatants and the CD25 expression in cultured PBMCs obtained from HIV-1+ individuals in presence of IL-2. The results showed a significant increases in RANTES production and in the expression of CD25+ in the cultures with IL-2 of PBMC obtained from HIV-1+ patients with a detectable viral load in comparison with both, HIV-1+ patients with no detectable viral loads and with healthy individuals. These results suggest that therapeutic IL-2 administered in addition to highly active anti-retroviral therapy (HAART) may contribute to increase the effect of this therapy by rising both RANTES production and CD25 expression only in HIV-1+ patients with detectable viral loads.

PMID: 16644491 [PubMed - in process]



















The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat.

Truettner JS, Suzuki T, Dietrich WD.

Department of Neurological Surgery, The Neurotrauma Research Center, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33136, USA.

Traumatic brain injury (TBI) initiates a cascade of cellular and molecular responses including both pro- and anti-inflammatory. Although post-traumatic hypothermia has been shown to improve outcome in various models of brain injury, the underlying mechanisms responsible for these effects have not been clarified. In this study, inflammation cDNA arrays and semi-quantitative RT-PCR were used to detect genes that are differentially regulated after TBI. In addition, the effect of post-traumatic hypothermia on the expression of selective genes was also studied. Rats (n = 6-8 per group) underwent moderate fluid-percussion (F-P) brain injury with and without hypothermic treatment (33 degrees C/3 h). RNA from 3-h or 24-h survival was analyzed for the expression of IL1-beta, IL2, IL6, TGF-beta2, growth-regulated oncogene (GRO), migration inhibitory factor (MIF), and MCP (a transcription factor). The interleukins IL-1beta, IL-2, and IL-6 and TGF-beta and GRO were strongly upregulated early and transiently from 2- to 30-fold over sham at 3 h, with normalization by 24 h. In contrast, the expressions of MIF and MCP were both reduced by TBI compared to sham. Post-traumatic hypothermia had no significant effect on the acute expression of the majority of genes investigated. However, the expression of TGF-beta2 at 24 h was significantly reduced by temperature manipulation. The mechanism by which post-traumatic hypothermia is protective may not involve a general genetic response of the inflammatory genes. However, specific genes, including TGF-beta2, may be altered and effect cell death mechanisms after TBI. Hypothermia differentially regulates certain

genes and may target more delayed responses underlying the secondary damage following TBI.

PMID: 15922484 [PubMed - in process]









 erase chain reaction in unstimulated PBMC and in PBMC incubated for 4h in the presence of concanavalin A (ConA) or phorbol 12-myristate 13-acetate plus ionomycin (PMA/I). Compared to unstimulated cells, stimulation with ConA and PMA/I increased the IL2 mRNA transcription in average by 300- and 20-fold, respectively. Nevertheless, no significant differences in IL2 transcription between the genotypes could be detected. These findings were confirmed by band shift studies using different oligonucleotides containing variations of the potential binding motif, which showed no differences in the gel mobility after incubation with nuclear extract containing GATA-3. The obtained results argue against an impact of this polymorphism on the IL2 transcription and the genetic disease resistance in sheep.





















ICAM-1 gene expression in endothelial cells: Effects on the inhibition of STAT3 phosphorylation.
Resveratrol suppresses IL-6-induced
Wung BS, Hsu MC, Wu CC, Hsieh CW.

Department of Applied Microbiology, National Chiayi University, Chiayi, Taiwan.

Resveratrol, a polyphenolic phytoaxelin present in red wine, has been suggested to protect against atherosclerosis and cardiovascular disease because of its antioxidant effects. Intercellular adhesion molecule (ICAM-1), induced by cytokines, has been hypothesized to play a role in the early events during atherosclerosis. In this study we tested the effects of resveratrol upon both IL-6-induced ICAM-1 gene expression and its underlying signaling pathways in endothelial cells (ECs). Resveratrol was found to inhibit both TNFalpha- and IL-6-induced ICAM-1 gene expression at the promoter, transcriptional and protein levels. Resveratrol also abrogates the tyr705 phosphorylation of STAT3 in IL-6-treated ECs, in a dose- and time-dependent manner. Although quercetin had similar effects, resveratrol showed higher inhibitory properties following 2-4 h pretreatments. Resveratrol has been shown to induce the activity of endothelial nitric oxide synthase (eNOS) and increase NO production. Consistent with this, the treatment of ECs with a NO donor (SNAP) reduces IL-6-induced STAT3 phosphorylation. Conversely, exposure of ECs to a NOS inhibitor reversed the effects of resveratrol upon IL-6-induced STAT3 phosphorylation. Furthermore, ECs transfected with constitutively active Rac1 (RacV12) showed increases in ICAM-1 promoter activity, intracellular reactive oxygen species (ROS) levels and STAT3 phosphorylation, and these increases were attenuated by resveratrol treatment. In summary, we demonstrate for the first time that resveratrol inhibits IL-6-induced ICAM-1 gene expression, in part, by interfering with Rac-mediated pathways via the attenuation of STAT3 phosphorylation. This study therefore provides important new insights that may contribute to the proposed beneficial effects of resveratrol in endothelial responses to cytokines during inflammation.

PMID: 16150460 [PubMed - as supplied by publisher]


















Bradykinin mimics ischemic preconditioning by generating reactive oxygen species (ROS). To identify intermediate steps leading to ROS generation, rabbit cardiomyocytes were incubated in reduced MitoTracker Red that becomes fluorescent after exposure to ROS. Fluorescence intensity in treated cells was expressed as % of that in paired untreated cells. Bradykinin (500nM) caused 51+/-16% increase in ROS generation (p<0.001). Co-incubation with either bradykinin B2 receptor blocker HOE140 (5 micro M) or free radical scavenger N-(2-mercaptopropionyl) glycine (1mM) prevented this increase confirming the response was receptor-mediated and ROS were actually being measured. Closing mitochondrial KATP (mKATP)channels with 5-hydroxydecanoate (5HD, 1mM) prevented increased ROS generation. Bradykinin-induced ROS generation was blocked by L-NAME (200 micro M) implicating nitric oxide as an intermediate. Blockade of guanylyl cyclase with ODQ (10 micro M) aborted bradykinin-induced ROS generation, but not that from diazoxide, a direct opener of mKATP channels. The PKG blocker 8-Br-cGMPS (25 micro M) eliminated bradykinin's effect. Conversely, direct activation of PKG with 8-pCPT-cGMP (100 micro M) increased ROS generation (39+/-15%, p<0.004) similar to bradykinin. This increase was blocked by 5HD. Finally, the nitric oxide donor SNAP (1 micro M)increased ROS by 34+/-6%. This increase was also blocked by 5HD. In intact rabbit hearts bradykinin (400nM) decreased infarction from 30.5+/-3.0% of the risk zone in control hearts to 11.9+/-1.4% (p<0.01). This protection was aborted by either L-NAME (200 micro M) or ODQ (2 micro M)(35.4+/-5.7% and 30.4+/-3.0% infarction, resp., pNS vs control). Hence, bradykinin preconditions through receptor-mediated production of nitric oxide which activates guanylyl cyclase. The resulting cGMP activates PKG that opens mKATP. Subsequent release of ROS triggers cardioprotection.