Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prevention of type 1 diabetes in NOD mice by 1,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] is accompanied by a T-helper (Th) 1/Th2 cytokine shift in the pancreas. The aim of this study was to investigate whether this immune shift also occurs outside of the pancreas and whether it is limited to autoantigen-specific immune responses. NOD mice treated with 1alpha,25(OH)2D3 (5 microg/kg every 2 days) or control vehicle were immunized with GAD65 (p524-543) or ovalbumin (OVA) in the rear footpads. First, we examined T-cell proliferation and cytokine production (via enzyme-linked immunosorbent assay) of draining lymph node cells in vitro with or without peptide rechallenge. Although no differences in proliferation were measured between control and 1alpha,25(OH)2D3-treated mice after in vitro GAD65 rechallenge, a marked shift in cytokine secretion profile was seen in 1alpha,25(OH)2D3-treated mice: interleukin-4 was increased (37 +/- 5 vs. 21 +/- 12 pg/ml in controls, P < 0.005), whereas gamma-interferon levels were decreased (6 +/- 3 vs. 9 +/- 3 ng/ml in controls, P < 0.05). This shift was absent in OVA-primed mice. Second, we measured cytokine profiles by reverse transcriptase-polymerase chain reaction in popliteal lymph nodes at different time points after priming with GAD65 or OVA in vivo. A marked Th1/Th2 shift occurred in 1alpha,25(OH)2D3-treated mice after in vivo priming with GAD65. Again, this shift was absent after OVA immunization. Finally, we measured cytokine profiles after rechallenge with a panel of autoantigens (GAD65, heat shock protein 65, insulin B-chain) and control antigens (OVA, keyhole limpet hemocyanine, myelin proteolipid protein, tetanus toxin) and confirmed the Th1/Th2 shift in autoantigen-injected mice but not in control antigen-injected mice. In conclusion, the immune deviation induced by 1alpha,25(OH)2D3 in NOD mice can also be induced in the peripheral immune system but is limited to pancreatic autoantigens.
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PMID:1alpha,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543). 1092 29

IL-17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the proinflammatory cytokines IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. To date, there are few data available on the agents that stimulate IL-17 production. We therefore investigated the in vitro IL-17 response to a variety of mitogens and antigens, and compared the IL-17 response to interferon-gamma (IFN-gamma), IL-4, IL-10 and TNF-alpha. In this study we used a type-0 antigen, tetanus toxoid (TT), a type-1 antigen, PPD from Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase-polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL-17-producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL-17, with the highest levels being produced by anti-CD3/anti-CD28 stimulation. The antigens TT and PPD significantly increased IL-17 mRNA expression over time, but failed to have such an effect at the protein level. IL-17 protein was also detectable in both antigen-specific (TT, SS. B) and non-specific T cell clones, but at levels lower than IFN-gamma. IL-17 production did not correlate with either the type-1 cytokine IFN-gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or protein level.
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PMID:Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls. 1101 16

Specific immune cell activation is a hallmark of infections and autoimmune disorders. Quantification of proliferative cell responses by (3)H-thymidine incorporation is a slow process and describes only one type of cellular reaction. We here investigated early immunological responses of purified human peripheral blood mononuclear cells to the direct stimulus alpha CD3 and antigen specific stimulation (human myelin basic protein (hMBP), tetanus toxoid, and influenza vaccine) and compared them to polyclonal LPS stimulation. Cytokine mRNA levels were quantified using real-time quantitative reverse transcriptase polymerase chain reaction (RT PCR) 4 h, 16 h, and 48 h after activation. Proliferation was measured 96 h after initiation of the cultures. Antigen specific responses were detected as early as 4 h after stimulation and followed different kinetics depending on the mode of activation. We demonstrated significant correlations of cytokine mRNA and protein expression for TNF alpha, IL10, and IFN gamma. Expression of IL2 mRNA at 16 h was correlated with proliferation indices at 96 h whereas IL4 mRNA levels were negatively correlated. Early cytokine mRNA expression in stimulated immune cells provides important functional data and is a powerful tool with which to study immunological reactions.
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PMID:Characterization of early immunological responses in primary cultures of differentially activated human peripheral mononuclear cells. 1115 May 44


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