Cytokines affect ion transport in primary cultured thick ascending limb of Henle's loop cells.
Tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) affect epithelial cell ion transport. However, the site of action along the nephron has not been elucidated fully for these cytokines. Thus, the effect of TNF and IL-1 on the ion transport function of primary cultured medullary thick ascending limb of Henle's loop (mTALH) cells was determined by measuring rubidium (86Rb) uptake. TNF, IL-1, and lipopolysaccharide (LPS), a known activator of cytokine production, inhibited 86Rb uptake by cultured mTALH cells after a 24-h incubation period but had no effect when incubated with the cells for 1 or 4 h. Furthermore, mTALH cells produced biologically active TNF after stimulation with LPS for 24 h, and the LPS-induced inhibition of 86Rb uptake was abolished in the presence of an anti-TNF antibody, suggesting that TNF produced by the mTALH cells acted in an autocrine manner to inhibit 86Rb uptake. The effects of LPS on 86Rb uptake also were inhibited by the cyclooxygenase inhibitor, indomethacin. As TNF increased prostaglandin E2 synthesis by cultured mTALH cells and as prostaglandin E2 also inhibited 86Rb uptake, LPS presumably inhibited 86Rb uptake by inducing a TNF-mediated increase in prostaglandin synthesis. These data demonstrate that a prostanoid produced by mTALH cells mediates the inhibitory effect of LPS and TNF on 86Rb uptake and imply that endogenous TNF inhibits ion fluxes in the mTALH via a prostaglandin-dependent mechanism.
Department of Pharmacology, New York Medical College, Valhalla 10595.
B A
BA
Escalante
N R
NR
Ferreri
C E
CE
Dunn
J C
JC
McGiff
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007477:Ions; D008070:Lipopolysaccharides / Q000494:pharmacology; D008138:Loop of Henle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D007477:Ions; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone