Tumor necrosis factor-α: regulation of renal function and blood pressure - PubMed (original) (raw)

Review

Tumor necrosis factor-α: regulation of renal function and blood pressure

Vanesa D Ramseyer et al. Am J Physiol Renal Physiol. 2013.

Abstract

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that becomes elevated in chronic inflammatory states such as hypertension and diabetes and has been found to mediate both increases and decreases in blood pressure. High levels of TNF-α decrease blood pressure, whereas moderate increases in TNF-α have been associated with increased NaCl retention and hypertension. The explanation for these disparate effects is not clear but could simply be due to different concentrations of TNF-α within the kidney, the physiological status of the subject, or the type of stimulus initiating the inflammatory response. TNF-α alters renal hemodynamics and nephron transport, affecting both activity and expression of transporters. It also mediates organ damage by stimulating immune cell infiltration and cell death. Here we will summarize the available findings and attempt to provide plausible explanations for such discrepancies.

Keywords: TNF receptor; TNF-α; blood pressure; hypertension; natriuresis; renal hemodynamics; septic shock; transport.

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Figures

Fig. 1.

Diagram representing the effects of increasing levels of TNF-α in renal function and the hypothetical effect on blood pressure. Increases of 1- to 2-fold in TNF-α are present in hypertension whereas increases of TNF-α >5 times are observed in septic shock. Dashed line represents a theoretical relationship between TNF-α levels and blood pressure. NO, nitric oxide; NOS3, nitric oxide synthase type 3; GFR, glomerular filtration rate; RBF, renal blood flow.

Fig. 2.

Cartoon showing the effects of TNF-α on ion transport in vitro in epithelial cells of the kidney. Effects of TNF-α in proximal tubular cells (A), in thick ascending limb cells (B), and in collecting duct cells (C). Red boxes and arrows represent pathways activated by TNF-α that are likely to increase Na reabsorption. Green boxes and arrows represent pathways activated by TNF-α that are likely to inhibit Na reabsorption. TNFR, TNF-α receptor; NHE3, Na/H exchanger type 3; NOS2, nitric oxide synthase type 2; ERK, extracellular signal-regulated kinases; Pi, phosphate; pGEF-H1, phosphorylated guanine nucleotide exchange factor-H1; ROCK, Rho-dependent kinase; MLCK, myosin light chain kinase; pMLC, phosphorylated myosin light chain; SF, actin stress fibers; NKCC2, Na-K-2Cl cotransporter; COX2, cyclooxygenase type 2; PGE2, prostaglandin type 2; CaSR, calcium-sensitive receptor; ANG II, angiotensin II; ENaC, epithelial Na channel; PKA, cAMP-dependent protein kinase; PI3K, phosphatidylinositol 3 kinase; SMase, sphingomyelinase; PKC, protein kinase C.

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Tumor necrosis factor-α: regulation of renal function and blood pressure - PubMed (original) (raw)