Concerted actions of IL-1beta inhibit Na+ absorption and stimulate anion secretion by IMCD cells.
Increasing evidence indicates that factors other than adrenocorticoid hormones can influence long-term regulation of Na+ transport by inner medullary collecting duct (IMCD) cells. We now report that, of 14 interleukins tested, only interleukin-1alpha (IL-1alpha) and IL-1beta inhibited Na+ transport by primary cultures of rat IMCD. IL-1beta reduced both basal and mineralocorticoid (MC)-stimulated Na+ transport by 50-70%; its effect on glucocorticoid (GC)-stimulated Na+ transport was significantly less. IL-1beta continued to blunt MC stimulation of Na+ transport even after it had been removed from the medium for 24 h. The onset of action to inhibit Na+ transport was within 20 min. The acute effect from the basolateral surface was greater than that from the apical surface, but the effect from each surface was additive. In addition to its inhibitory effect on Na+ transport, chronic IL-1beta exposure increased both basal and cAMP-stimulated anion secretion rates. IL-1beta had no acute effect on anion secretion. Monolayers chronically treated with IL-1beta had an increased capacity to secrete fluid, as predicted from its effects on ion transport. Inhibitors of cyclooxygenase did not blunt the actions of IL-1beta. Furthermore, IL-1beta did not produce a rise in intracellular Ca2+. These results suggest novel signaling pathways induced by IL-1beta regulating Na+ and Cl- transport by the IMCD.
Husted
R F
RF
Laboratory of Epithelial Transport, Department of Internal Medicine, University of Iowa and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
Zhang
C
C
Stokes
J B
JB
D000042:Absorption / Q000187:drug effects; D000818:Animals; D000838:Anions / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000493:pharmacokinetics*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology
D000838:Anions; D000906:Antibodies; D007375:Interleukin-1; D007378:Interleukins; D008901:Mineralocorticoids; D016212:Transforming Growth Factor beta; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium