IL-1 beta gene expression in B cells derived from the murine MRL/lpr model of lupus.
The MRL/lpr model of SLE resembles human lupus in its various immunopathologic characteristics including the presence of high-level IgG and anti-DNA antibody production and multisystem organ involvement (nephritis, arthritis, and vasculitis). Our previous studies have shown that IL-1 overactivity in B cells plays a potentially important role in driving IgG and autoantibody production. However, the underlying mechanisms determining IL-1 overactivity are poorly understood. We studied IL-1 beta gene expression and transcriptional rates in B cells derived from old and young MRL/lpr, MRL/+ +, and non-autoimmune control mice using semi-quantitative RT-PCR and the nuclear run-on assay. RT-PCR demonstrated increased steady-state IL-1 beta gene expression in B cells derived from old MRL/lpr mice as compared to either young MRL/lpr or control mice. Furthermore, IL-1 beta gene expression in B cells was associated with the presence of the lpr mutation because heightened IL-1 beta message was observed in RNA obtained from MRL/lpr but not MRL/+ + B cells. IL-1 beta transcriptional rates measured by the nuclear run-on assay were very similar in B cells from old and young MRL/lpr and control mice. These observations suggest that IL-1 overactivity in B cells obtained from old diseased MRL/lpr results from heightened IL-1 beta message, is associated with the presence of the lpr mutation, and is likely to reflect post-transcriptional stabilization of IL-1 beta mRNA.
Mao
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Division of Nephrology, New England Medical Center, Boston, MA02111, USA.
Singh
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AK
D000375:Aging / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000235:genetics*; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr
D007375:Interleukin-1