Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1beta-treated human peritoneal mesothelial cells.
The peritoneal mesothelium acts as a regulator of serosal responses to injury, infection, and neoplastic diseases. After inflammation of the serosal surfaces, proinflammatory cytokines induce an "activated" mesothelial cell phenotype, the mitochondrial aspect of which has not previously been studied. After incubation of cultured human peritoneal mesothelial cells with interleukin (IL)-1beta for 48 h, respiratory activity of suspended cells was analyzed by high-resolution respirometry. Citrate synthase (CS) and lactate dehydrogenase (LDH) activities were determined by spectrophotometry. Treatment with IL-1beta resulted in a significant decline of respiratory capacity (p < 0.05). Respiratory control ratios (i.e., uncoupled respiration at optimum carbonyl cyanide p-trifluoromethoxyphenylhydrazone concentration divided by oligomycin inhibited respiration measured in unpermeabilized cells) remained as high as 11, indicating well-coupled mitochondria and functional integrity of the inner mitochondrial membrane. Whereas respiratory capacities of the cells declined in proportion with decreased CS activity (p < 0.05), LDH activity increased (p < 0.05). Taken together, these results indicate that IL-1beta exposure of peritoneal mesothelial cells does not lead to irreversible defects or inhibition of specific components of the respiratory chain, but is associated with a decrease of mitochondrial content of the cells that is correlated with an increase in LDH (and thus glycolytic) capacity.
Stadlmann
Sylvia
S
Department of Pathological Anatomy, University Hospital Innsbruck, Austria.
Renner
Kathrin
K
Pollheimer
Juergen
J
Moser
Patrizia Lucia
PL
Zeimet
Alain Gustave
AG
Offner
Felix Albert
FA
Gnaiger
Erich
E
D019069:Cell Respiration / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010538:Peritonitis / Q000378:metabolism*; D014475:Uncoupling Agents / Q000378:metabolism
D007375:Interleukin-1; D014475:Uncoupling Agents; D007770:L-Lactate Dehydrogenase; D002950:Citrate (si)-Synthase