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Abstract: SA-PO1079

Macrophage COX-2 Deletion Activates Renal T Cells and Transporter Activity in Response to High Salt Intake

Session Information

Category: Hypertension

  • 1101 Hypertension: Basic and Experimental - Neural and Inflammatory Mechanisms

Authors

  • Zhang, Ming-Zhi, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Li, Zhilian, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Chung, Sungjin, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wang, Yinqiu, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Niu, Aolei, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Fan, Xiaofeng, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Harris, Raymond C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Chronic use of non-selective NSAIDs or selective cyclooxygenase-2 (COX-2) inhibitors leads to increases in blood pressure. Recently, the immune system has been shown to play an important role in the pathogenesis of hypertension. Both interleukin-17 (IL-17) and interferon γ (IFNγ) production by aberrantly activated effector T cells contribute to angiotensin II-mediated and DOCA/salt-induced hypertension. Bone marrow-derived cells are known to be a rich source of prostaglandins and COX-2-derived prostaglandins modulate and affect both macrophage and T cell function. We recently reported that bone marrow cell COX-2 promotes non-inflammatory, alternatively activated M2 phenotypes in renal macrophages, and bone marrow cell COX-2 deletion led to salt-sensitive hypertension. In the current studies we investigated the potential activation of renal T lymphocytes in response to high salt intake when macrophage COX-2 is deleted.

Methods

Male COX-2f/f (WT) and CD-11b Cre; COX-2f/f (macrophage COX-2-/-) mice (FVB background) were fed a high salt diet (8% NaCl) for 5 weeks. Renal macrophages and T lymphocytes were isolated with CD11b and CD90.1 microbeads, respectively.

Results

Renal macrophage COX-2 mRNA was efficiently deleted in macrophage COX-2-/-. Renal macrophages from high salt-treated macrophage COX-2-/- mice expressed increased IL-23, known to activate Th17 cells. In kidneys from high salt-treated macrophage COX-2-/- mice, there were increased CD4-positive T cells, which expressed increased IFNγ and IL-17, but there were decreased regulatory T cells (Tregs). Cleaved epithelial sodium channel (ENaC) levels, an indicator of its activation, were much higher in high salt treated macrophage COX-2-/- mice.

Conclusion

These results suggest that deletion of macrophage COX-2 leads to aberrant activation of T lymphocytes, with subsequent increased production of IL-17 and IFNγ and activation of sodium transporters in response to chronic salt intake and may contribute to salt-sensitive hypertension.

Funding

  • NIDDK Support