Aldosterone Acts Directly On T Cells, and Promotes Production of Inflammatory Cytokines
Department of Developmental, Molecular and Chemical Biolgy, Tufts University Medical School, Boston.
Meeting: 2015 American Transplant Congress
Abstract number: D21
Keywords: T cells
Session Information
Session Name: Poster Session D: Costimulation and Signaling in Lymphocytes
Session Type: Poster Session
Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Aldosterone is a mineralocorticoid hormone involved in the regulation of blood electrolyte concentration, blood pressure and blood volume. The primary receptor for aldosterone is the mineralocorticoid receptor (MR), an intracellular receptor that has previously been thought to be expressed primarily in distal tubules and collecting ducts in the kidney. However, this view of aldosterone activity has been challenged during the past few years, with numerous reports showing MR expression in tissues other than kidneys, including blood vessels, brain, heart and lymphocytes. Aldosterone plays a key role in the development of both congestive heart failure and progressive kidney dysfunction. Inhibitors of aldosterone are currently being tested in clinical trials for efficacy in preventing toxicity in response to calcineurin inhibitors. Thus, the effect of aldosterone, and its inhibitors on the immune response, is of interest in understanding kidney dysfunction following transplantation. To clarify the potential for T cells to respond directly to aldosterone, we examined expression of MR in CD3+ T cells purified through positive magnetic selection. We found that T cells express MR transcripts, supporting the hypothesis that aldosterone may directly act on T cells to modulate T cell activation and proliferation. When CD4 T cells are activated, the expression level of CD69 as reflected by median fluorescent intensity was increased when T cells were treated with aldosterone when compared with vehicle control. These effects were reversed when cells were exposed to aldosterone inhibitors, eplerenone or spirnolactone, indicating that aldosterone has a direct effect on the activation of T cells. We next treated mice systemically with aldosterone, and quantified expression of the cytokines IL-4, IFN-γ, IL-6, IL-17, TGF- β and IL-13 in splenocytes. Both IL-17 and IFN-γ expression were systemically up-regulated in mice treated with aldosterone compared with placebo. Expression of IL-4 was not significantly affected. This suggests aldosterone increases the expression of pro-inflammatory cytokines in vivo. In addition, we observed a significantly decreased frequency of regulatory T cells from mice treated with aldosterone, when compared with placebo treated control. Together these data suggest that aldosterone has significant pro-inflammatory effects which may affect the development of progressive kidney dysfunction following transplantation.
To cite this abstract in AMA style:
Bagley J, Begum S, Iacomini J. Aldosterone Acts Directly On T Cells, and Promotes Production of Inflammatory Cytokines [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/aldosterone-acts-directly-on-t-cells-and-promotes-production-of-inflammatory-cytokines/. Accessed October 15, 2024.« Back to 2015 American Transplant Congress