Induced upregulation of IL-1, IL-1RA and IL-1R type I gene expression by Schwann cells.
We analyzed two distinct phenotypes of Schwann cells (SC), non-differentiated and differentiated, for their ability to produce IL-1alpha and IL-1beta, and to express message for IL-1 receptor antagonist (IL-IRA) and IL-1R type I, in vitro. SC were stimulated with: lipopolysaccharide (LPS), products of activated splenocytes (ASP), products from LPS stimulated SC (SCP), rat recombinant IL-1beta (rrIL-1beta) or dexamethasone. IL-1alpha, IL- 1beta and IL-1RA mRNA levels were highly upregulated after stimulation with LPS, ASP, SCP or rrIL-1beta. SC constitutively expressed low levels of message for IL-1alpha and IL-1beta but not IL-1RA. Specific mRNAs for both IL-1 isotypes were highly upregulated 2 to 4 h after LPS stimulation and then decreased and were undetectable by 24 h. IL-1RA mRNA was detectable after 6 h of LPS stimulation and was maximally upregulated at 24 h. IL-1 gene expression was inducible in both SC phenotypes. IL-1beta could be detected by immunofluorescence in SC, one to three days after LPS stimulation. At the same time IL-1 bioactivity was maximal in SC supernatants. Treatment with either SCP, rrIL-1beta or dexamethasone induced upregulation of IL-1R type I mRNA with maximal expression between 2 to 4 h, in SC. Inducible expression of genes for IL-1alpha, IL-1beta, IL-1RA and IL-1R type I in both differentiated and non-differentiated SC suggest autocrine and paracrine regulation of IL-1 by SC.
Skundric
D S
DS
Department of Neurology, Division of Neuroimmunology, Wayne State University, Detroit Medical Center, MI, USA.
Bealmear
B
B
Lisak
R P
RP
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000235:genetics* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011994:Recombinant Proteins; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D014158:Transcription, Genetic
D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D003907:Dexamethasone