Role of mitogen-activated protein kinase cascades in inducible nitric oxide synthase expression by lipopolysaccharide in a rat Schwann cell line.

It is well known that the mitogen-activated protein kinase (MAPK) signal transduction pathways is involved in the regulation of inducible nitric oxide synthase (iNOS) in many cellular systems. However, sufficient information describing the role of MAPKs on iNOS expression in rat Schwann cells (SCs) is lacking. Therefore the paper was sought to investigate the role of MAPK cascades in iNOS expression following treatment of lipopolysaccharide (LPS) in a rat Schwann cell line RSC 96. Reverse transcriptase-PCR analysis (RT-PCR) and immunocytochemical staining were performed to detect iNOS expression following LPS induction. Next RT-PCR and Western blot analysis were employed to study expression of iNOS after using inhibitors selective for ERK (PD98059), JNK/SAPK (SP600125) and p38 (SB202190). The production of nitric oxide (NO) was measured by nitrate reductase method. LPS could significantly induce the expression of iNOS located in the cytoplasm in RSC 96 with a concentration- and time-dependent manner. Administration of inhibitors individually and combinations of the three inhibitors at micromolar concentrations suppressed the expression of iNOS and the production of NO. Based on these observations, it is proposed that LPS may activate the rat Schwann cell line RSC 96 to express iNOS and release NO via the MAPK signal transduction pathways.