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Updated: May 27, 2026
10:15
Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
Eicosanoids and tumor necrosis factor-alpha in the kidney
Nicholas R Ferreri1, Shoujin Hao, Paulina L Pedraza
1Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. nick_ferreri@nymc.edu
Prostaglandins & Other Lipid Mediators
|November 22, 2011
Summary
The thick ascending limb of Henle
Area of Science:
- Nephrology
- Molecular Biology
- Hypertension Research
Background:
- The thick ascending limb of Henle's loop (TAL) metabolizes arachidonic acid (AA) via cytochrome P450 (CYP450) and cyclooxygenase (COX) pathways.
- TAL is implicated in salt-sensitive hypertension, with CYP450 products inhibiting ion transport.
- COX-2 is constitutively present in TAL and upregulated by stimuli.
Purpose of the Study:
- To investigate the role of tumor necrosis factor (TNF) in medullary TAL (mTAL) cells.
- To determine the effects of TNF on mTAL function and ion transport.
- To elucidate the molecular mechanisms linking calcium-sensing receptor (CaR), TNF, and COX-2 in mTAL.
Main Methods:
- Investigated TNF production and localization in mTAL cells using Tamm-Horsfall glycoprotein as a marker.
- Examined the colocalization of CaR and COX-2 in the TAL.
- Assessed the impact of TNF on ⁸⁶Rb uptake (a measure of natriuresis) and Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) expression/trafficking in mTAL cells.
Main Results:
- Activation of CaR in mTAL cells induces TNF-dependent COX-2 expression and prostaglandin E₂ (PGE₂) synthesis.
- TNF produced by mTAL cells inhibits ⁸⁶Rb uptake via an autocrine and COX-2-dependent mechanism.
- These inhibitory effects are associated with reduced NKCC2 expression and trafficking.
Conclusions:
- mTAL cells produce TNF, contributing to autocrine regulation of ion transport.
- CaR activation stimulates TNF-mediated COX-2 expression and PGE₂ synthesis in mTAL.
- TNF signaling in mTAL inhibits natriuresis by downregulating NKCC2, potentially contributing to salt-sensitive hypertension.
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