Lysophosphatidylcholine up-regulates IL-1 beta-induced iNOS expression in rat mesangial cells.
BACKGROUND
Nitric oxide (NO), a simple molecule synthesized from L-arginine by NO synthases (NOS), has been identified to play an important role in cell communication, cell defense and cell injury. Several studies have shown that glomeruli from rats with immune-mediated glomerular inflammation have increased production of NO. Recently, it was also reported that inducible NOS (iNOS) is localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased human glomeruli. On the other hand, while oxidized low density lipoprotein (ox-LDL) has been suggested to be related to progression of glomerular disease, the mechanism remains unknown. We investigated the effect of lysophosphatidylcholine (LPC), a modified phospholipid produced during LDL oxidation, on iNOS expression in rat mesangial cells.


RESULTS
Treatment of mesangial cells with interleukin-1 beta (IL-1 beta) induced iNOS activity measured as nitrite levels in cell culture supernatants. Treatment with LPC had no effect. In contrast, coincubation with LPC and IL-1 beta resulted in a markedly higher nitrite content compared to that after incubation with IL-1 beta alone. Western blot analysis revealed that LPC caused a significant increase in the formation of iNOS protein in the presence of IL-1 beta.


CONCLUSIONS
These findings suggest that LPC may contribute to progression of glomerular inflammation by augmenting IL-1 beta-induced iNOS expression.
Third Department of Internal Medicine, Wakayama Medical College, Japan. hotani@wakayama-med.ac.jp
M
M
Taniuchi
H
H
Otani
N
N
Kodama
Y
Y
Tone
M
M
Sakagashira
Y
Y
Yamada
M
M
Mune
S
S
Yukawa
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007375:Interleukin-1 / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D051381:Rats
D007375:Interleukin-1; D008244:Lysophosphatidylcholines; D009573:Nitrites; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat