Effects of natural and recombinant interleukin-1 alpha and -beta on cytosolic free calcium in human and murine fibroblasts.
Changes in the concentration of cytosolic free calcium ((Ca2+)i) in response to purified blood monocyte IL-1 and human rIL-1 alpha and rIL-1 beta (17.5 kDa) were measured in murine L-M fibroblasts and in human foreskin fibroblasts using the fluorescent Ca2+ indicator, fura-2. In L-M fibroblasts, each of these IL-1 species, but not a recombinant 24-kDa precursor of the predominant IL-1 beta, produced a prompt, dose-related, and transient increase in (Ca2+)i. The effect was smaller but not eliminated when the cells were stimulated in EGTA-containing calcium, suggesting that the rise in (Ca2+)i was due to influx from both intracellular and extracellular Ca2+ pools. In human fibroblasts, however, the (Ca2+)i increased gradually, reaching a maximum after 1 hr of incubation with IL-1 and returning slowly to near basal levels in the following 2 hr. In contrast to the L-M cells, this accumulation of Ca2+ was abolished by EGTA, suggesting that in human fibroblasts, Ca2+ is mobilized solely from the extracellular space. Addition of the Ca2+ channel blockers verapamil and nifedipine was ineffective. IL-1 alpha and IL-1 beta both induced a dose-related increase in prostaglandin E2, but only in the human fibroblasts. These findings indicate that an increase in (Ca2+)i may be an important second mediator by which IL-1 initiates cell activation, but the signal may differ between cells.
Bouchelouche
P N
PN
Department of Clinical Chemistry and Medicine C, Herlev Hospital, University of Copenhagen, Denmark.
Reimert
C
C
Bendtzen
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D010455:Peptides; D011994:Recombinant Proteins; D014700:Verapamil; D015232:Dinoprostone; D002118:Calcium