Concerted actions of IL-1β inhibit Na+ absorption and stimulate anion secretion by IMCD cells

Abstract

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-1α (IL-1α) and IL-1β inhibited Na+ transport by primary cultures of rat IMCD. IL-1β reduced both basal and mineralocorticoid (MC)-stimulated Na+ transport by 50-70%; its effect on glucocorticoid (GC)-stimulated Na+ transport was significantly less. IL-1β 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-1β exposure increased both basal and cAMP-stimulated anion secretion rates. IL-1β had no acute effect on anion secretion. Monolayers chronically treated with IL-1β 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-1β. Furthermore, IL-1β did not produce a rise in intracellular Ca2+. These results suggest novel signaling pathways induced by IL-1β regulating Na+ and Cl- transport by the IMCD.