AJP - Cell Physiology, Vol 263, Issue 5 C1073-C1080, Copyright © 1992 by American Physiological Society
Effects of intracellular ions on interleukin-1 beta production by lipopolysaccharide-activated human monocytes
U. Orlinska and R. C. Newton
Du Pont Merck Pharmaceutical, Inflammatory Diseases Research, Glenolden, Pennsylvania 19036.
Following the observation that interleukin 1 beta (IL-1 beta) production in
lipopolysaccharide (LPS)activated monocytes increases in concert with a
rise in intracellular pH (pHi), the role of ion transport in IL-1 beta
production was investigated. The amiloride analogue
5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na(+)-H+
antiporter, inhibited extracellular IL-1 beta. The replacement of Na+ in
the culture medium with sucrose or choline chloride also prevented monocyte
activation. The sodium ionophore monensin, in doses from 100 pM to 1
microM, potentiated LPS-stimulated extracellular IL-1 beta when compared
with LPS alone. In the absence of LPS activation, monensin by itself at 10
nM stimulated IL-1 beta production to 63%. EIPA at 10 microM inhibited the
Na+ influx, the rise in pHi, and intra- and extracellular IL-1 beta
production in activated monocytes; this inhibition was reversed by 10 nM
monensin. In the absence of bicarbonate, or in the presence of 10 microM
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, the pHi of activated
monocytes and the total protein synthesis did not change, but the
production of IL-1 beta was inhibited. The data suggest that the stimulated
influx of Na+ via the Na(+)-H+ antiporter regulates both pHi and IL-1 beta
production in LPS-activated monocytes. The requirement for bicarbonate
indicates an additional mechanism(s), separate from the modulation of pHi
and intracellular Na+.
