Lupus Nephritis Clinical Trial
Official title:
The Mechanisms and Significances of Synergistic Effects of Mycophenolic Acid and Lipopolysaccharide on Interleukin-1β Secretion by Mononuclear
To determine the mechanisms and significances of synergistic effects of mycophenolic acid and LPS on IL-1β secretion by mononuclear
Mycophenolate mofetil (MMF), which inhibits T and B lymphocyte proliferation, is widely used
to treat a variety of autoimmune diseases, such as systemic lupus erythematosus (SLE) and
lupus nephritis (LN). We are the first to show that mycophenolic acid (MPA), the active
metabolite of MMF, in association with lipopolysaccharide (LPS), is able to promote the
secretion of interleukin (IL)-1β, which contradicts the traditional conception that
immunosuppressants inhibit the secretion of inflammatory factors.
In this study, we first determined the effects of MPA in association with LPS on IL-1β
production. Then, we explored whether the synergized effect on IL-1β production was mediated
through the nuclear factor (NF)-κB pathway that produces more pro-IL-1β, or through the
triggering of NLRP3 inflammasome that leads to enhanced activation of caspase-1 and
accelerated degradation of pro-IL-1β into mature IL-1β.
This study is not only conducive to clarify the mechanisms, signal transduction pathways and
potential clinical significances of IL-1β production in LPS and MPA combined treatment, but
also to provide experimental data as well as theoretical rationales for more effective and
more logical immunosuppressive protocols.
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Observational Model: Case-Only, Time Perspective: Cross-Sectional
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