AT1R blockade reduces IFN-γ production in lymphocytes in vivo and in vitro
| Autor: | Arjang Djamali, Lynn M. Jacobson, Debra A. Hullett, Jenifer Sprague, Rebecca J. Muehrer, Jon A. Weidanz, Thomas J. Thekkumkara, Bryan N. Becker, Vaughan Wittman, Maurizio Chiriva-Internati |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
peripheral blood lymphocytes business.industry ELISPOT Lymphocyte kidney transplantation Lymphocyte proliferation angiotensin II lymphocyte proliferation cytotoxic T-lympocyte line Angiotensin II angiotensin receptor blockers medicine.anatomical_structure Endocrinology Losartan In vivo Nephrology Internal medicine medicine Cytotoxic T cell Interferon gamma business IFN-γ chronic allograft nephropathy medicine.drug |
| Zdroj: | Kidney International. 67(6):2134-2142 |
| ISSN: | 0085-2538 |
| DOI: | 10.1111/j.1523-1755.2005.00318.x |
| Popis: | AT1R blockade reduces IFN-γ production in lymphocytes in vivo and in vitro.BackgroundType 1 angiotensin II (Ang II) receptor (AT1R) signaling induces proinflammatory responses. Recent studies suggest that T lymphocytes express AT1R; yet the effects of Ang II binding to AT1R on T cells are poorly understood. We examined the effect of AT1R blockade on release of the proinflammatory cytokine, interferon-gamma (IFN-γ) by human lymphocytes in vivo and in vitro.MethodsWe used an AT1R blocker losartan in a randomized clinical trial in kidney transplant recipients over a 12-month period [AT1R blocker (N = 11) and control (N = 10)]. Peripheral blood lymphocytes, isolated from both cohorts, were analyzed by enzyme-linked immunosorbent spot assays (ELISPOT) analyses and real-time reverse transcription-polymerase chain reaction (RT-PCR) to enumerate IFN-γ producing T cells and IFN-γ mRNA levels. The effects of AT1R blockade in vitro were assessed using human alloreactive T cells and an IFN-γ producing human cytotoxic T-lymphocyte line. Alloreactive T cells were treated with losartan or candesartan and enzyme-linked immunosorbant assay (ELISA) was used to measure IFN-γ protein release. The cytotoxic T-lymphocyte line also was AT1R blocker–treated prior to determining IFN-γ producing cells by intracellular cytokine staining.ResultsThe AT1R blocker cohort had a significant decrease in IFN-γ producing peripheral blood lymphocytes (P≤ 0.05 for each time point) and IFN-γ mRNA levels (P = 0.01 vs. control patients). Losartan also decreased IFN-γ production (P < 0.001) in purified alloreactive T cells in vitro as did candesartan. Moreover, Ang II amplified IFN-γ generation (P < 0.05) in alloreactive T cells while AT1R blocker treatment inhibited Ang II's effect (P < 0.04). AT1R blocker treatment furthermore also inhibited IFN-γ production in the cytotoxic T-lymphocyte line.ConclusionAT1R blockers may have a clinically relevant immunomodulatory role by blocking IFN-γ production in T cells. |
| Databáze: | OpenAIRE |
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