Interleukin-1 alpha, but not interleukin-1 beta, is a co-mitogen for neonatal rat Schwann cells in vitro and acts via interleukin-1 receptors.
The culture of neonatal rat Schwann cells (SC) with unfractionated cytokines induces an increase in SC proliferation. Previous studies demonstrated that while incubation of SC with interleukin-1(IL-1) does not result in enhanced SC mitogenesis, a mixture of antibodies to IL-1 alpha plus IL-1 beta inhibits cytokine-induced proliferation. We undertook the current studies to: (i) confirm that neither isoform of IL-1 directly causes SC proliferation; (ii) determine if there is a difference in the effect of antibodies to IL-1 alpha versus IL-1 beta; and (iii) determine if IL-1 contribution to cytokine-induced proliferation of SC is mediated via IL-1 receptors. IL-1 alpha or IL-1 beta from several sources, over a wide range of concentrations, failed to induce SC proliferation. Polyclonal antibodies to IL-1 alpha from several suppliers and a monoclonal antibody to IL-1 alpha inhibited SC proliferation, whereas similar antibodies to IL-1 beta had no effect on cytokine-induced SC proliferation. Addition of excess IL-1 alpha to an incubation mixture of unfractionated cytokines plus anti-IL-1 alpha abolished the inhibitory effect of the antibodies. Addition of IL-1 receptor antagonist (IL-1 Ra) to unfractionated cytokines inhibited SC proliferation. Therefore, while neither IL-1 alpha nor IL-1 beta is a solitary mitogen for neonatal rat SC, IL-1 alpha but not IL-1 beta acts as a co-mitogen. Moreover, IL-1 alpha seems to exert its co-mitogenic effect via receptors for IL-1.
Lisak
R P
RP
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201.
Bealmear
B
B
Ragheb
S
S
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012583:Schwann Cells / Q000187:drug effects* / Q000502:physiology; D012795:Sialoglycoproteins / Q000494:pharmacology
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008934:Mitogens; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins