Involvement of phospholipase A2 and lipoxygenase in lipopolysaccharide-induced inducible nitric oxide synthase expression in glial cells

✍ Scribed by Je-Seong Won; Yeong-Bin Im; Mushfiquddin Khan; Avtar K. Singh; Inderjit Singh

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 353 KB
• Volume: 51
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20178

✦ Synopsis

Abstract

The present study underlines the importance of phospholipase A~2~ (PLA~2~)‐ and lipoxygenase (LO)‐mediated signaling processes in the regulation of inducible nitric oxide synthase (iNOS) gene expression. In glial cells, lipopolysaccharide (LPS) induced the activities of PLA~2~ (calcium‐independent PLA~2~; iPLA~2~ and cytosolic PLA~2~; cPLA~2~) as well as gene expression of iNOS. The inhibition of cPLA~2~ by methyl arachidonyl fluorophosphates (MAFP) or antisense oligomer against cPLA~2~ and inhibition of iPLA~2~ by bromoenol lactone reduced the LPS‐induced iNOS gene expression and NFκB activation. In addition, the inhibition of LO by nordihydroguaiaretic acid (NDGA; general LO inhibitor) or MK886 (5‐LO inhibitor), but not baicalein (12‐LO inhibitor), completely abrogated the LPS‐induced iNOS expression. Because NDGA could abrogate the LPS‐induced activation of NFκB, while MK886 had no effect on it, LO‐mediated inhibition of iNOS gene induction by LPS may involve an NFκB‐dependent or ‐independent (by 5‐LO) pathway. In contrast to LO, however, the cyclooxygenase (COX) may not be involved in the regulation of LPS‐mediated induction of iNOS gene because COX inhibition by indomethacin (general COX inhibitor), SC560 (COX‐1 inhibitor), and NS398 (COX‐2 inhibitor) affected neither the LPS‐induced iNOS expression nor activation of NFκB. These results indicate a role for cPLA~2~ and iPLA~2~ in LPS‐mediated iNOS gene induction in glial cells and the involvement of LO in these reactions. © 2005 Wiley‐Liss, Inc.