Inadequate activation of the Mineralocorticoid Receptor (MR) promotes hypertension, inflammation and fibrosis. Neutrophil Gelatinase- Associated Lipocalin (NGAL), a pro-inflammatory/fibrotic glycoprotein, is a direct target of the MR in cardiovascular cells, and is increased in immune cells during inflammation. Recently, we demonstrated that NGAL is crucial for the hypertensive and pro-fibrotic effects of the nephrectomy-aldosteronesalt (NAS) challenge in mice. However, the specific cell types that modulate NGAL production during aldosterone-dependent hypertension are still unknown. The aim of this study was to characterize NGAL expression in mouse immune cells, and to study the effect of MR activation on NGAL and pro-inflammatory cytokines expression in dendritic cells (DCs).

Male C57Bl6 mice were submitted to 28 days of NAS challenge (200μg/kg/d). CD4⁺, CD8⁺ T cells, B cells, DCs and Macrophages (Mø) were sorted from spleen. DCs and Mø were cultured from WT and NGAL-KO mice and treated with aldosterone (100nM) for 24h. NGAL and cytokines mRNAs abundance was measured by RT-qPCR.

NAS treatment induced a selective increase in the recruitment of activated-CD8⁺ cells, B cells and granulocytes in lymph nodes. NGAL abundance was higher in PBMC, DCs and Mø, and further increased in NAS mice (<3-fold vs. Sham). In vitro MR activation by aldosterone in DCs induced an upregulation of NGAL and cytokines involved in the adaptive immune response (TGF-β1, IL-23). Interestingly, the absence of NGAL in DCs prevented this increase.

MR activation and subsequent NGAL induction in DCs could play a pivotal role in the inflammation observed during aldosterone-dependent hypertension.

The author hereby declares no conflict of interest