Study summary · research use only
BAM15, a Mitochondrial Uncoupling Agent, Attenuates Inflammation in the LPS Injection Mouse Model: An Adjunctive Anti-Inflammation on Macrophages and Hepatocytes
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study examined BAM15, a mitochondrial uncoupling agent, in a lipopolysaccharide (LPS) injection mouse model and in mouse macrophage (RAW246.7) and hepatocyte (Hepa 1-6) cell lines. Pretreatment with BAM15 in LPS-stimulated macrophages was associated with reduced inflammatory cytokines (IL-6, TNF-α, IL-10), downregulated M1 polarization genes (iNOS, IL-1β), upregulated M2 polarization genes (Arg1, FIZZ), and decreased cell energy status; similar decreases in IL-6, TNF-α, IL-10, and iNOS expression and cell energy were observed in hepatocytes. In LPS-administered mice, BAM15 was associated with reduced serum and tissue cytokines, reduced liver enzymes and serum creatinine, increased phosphorylated αAMPK in the liver, and reduced inflammatory monocytes/macrophages (Ly6C+ve, CD11b+ve) in the liver, as measured by Western blot and flow cytometry.
Abstract
Controlof immune responses through the immunometabolism interference is interesting for sepsis treatment. Then, expression of immunometabolism-associated genes and BAM15, a mitochondrial uncoupling agent, was explored in a proinflammatory model using lipopolysaccharide (LPS) injection. Accordingly, the decreased expression of mitochondrial uncoupling proteins was demonstrated by transcriptomic analysis on metabolism-associated genes in macrophages (RAW246.7) and by polymerase chain reaction in LPS-stimulated RAW246.7 and hepatocytes (Hepa 1-6). Pretreatment with BAM15 at 24 h prior to LPS in macrophages attenuated supernatant inflammatory cytokines (IL-6, TNF-α, and IL-10), downregulated genes of proinflammatory M1 polarization (iNOS and IL-1β), upregulated anti-inflammatory M2 polarization (Arg1 and FIZZ), and decreased cell energy status (extracellular flux analysis and ATP production). Likewise, BAM15 decreased expression of proinflammatory genes (IL-6, TNF-α, IL-10, and iNOS) and reduced cell energy in hepatocytes. In LPS-administered mice, BAM15 attenuated serum cytokines, organ injury (liver enzymes and serum creatinine), and tissue cytokines (livers and kidneys), in part, through the enhanced phosphorylated αAMPK, a sensor of ATP depletion with anti-inflammatory property, in the liver, and reduced inflammatory monocytes/macrophages (Ly6C +ve, CD11b +ve) in the liver as detected by Western blot and flow cytometry, respectively. In conclusion, a proof of concept for inflammation attenuation of BAM15 through metabolic interference-induced anti-inflammation on macrophages and hepatocytes was demonstrated as a new strategy of anti-inflammation in sepsis.
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