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Mycophenolic acid inhibits the phosphorylation of NF-κB and JNKs and causes a decrease in IL-8 release in H2O2-treated human renal proximal tubular cells
- Source :
-
Chemico-Biological Interactions . May2010, Vol. 185 Issue 3, p253-262. 10p. - Publication Year :
- 2010
-
Abstract
- Abstract: Ischaemia-reperfusion injury is a common occurrence in renal transplantation and may affect the long-term survival of the allograft. Oxidative stress may play a crucial role in this, with reactive oxygen species formed during reperfusion causing direct cellular damage as well as activating pro-inflammatory pathways. A human proximal tubule cell line (HK-2) was subjected to hydrogen peroxide (H2O2) stress that resulted in phosphorylation of c-jun N-terminal kinases (JNKs) and the transcription factor NF-κB at Ser276, both of which have been associated with inflammation. Interleukin (IL)-8 production also increased upon H2O2 stimulation. Pre-incubation of the cells with mycophenolic acid (MPA) resulted in reduced phosphorylation of both JNKs and NF-κB, and reduced IL-8 release in H2O2-stimulated HK-2 cells. MPA also reduced the H2O2-induced phosphorylation of p38 MAP (mitogen-activated protein) kinase, the extracellular-signal regulated kinase 1/2 (ERK1/2), Akt kinase and the transcription factor CREB (cyclic AMP response element binding protein). In rat kidneys subjected to ischaemia-reperfusion, an increase in both pJNK1/2 and pNF-κB was observed, which was reduced in kidneys obtained from mycophenolate mofetil (MMF)-treated rats. These results suggest that MPA may inhibit pro-inflammatory responses in the kidney by inhibiting activation of pro-inflammatory molecules in both the kidney and human renal proximal tubular cells subjected to oxidative stress. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00092797
- Volume :
- 185
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Chemico-Biological Interactions
- Publication Type :
- Academic Journal
- Accession number :
- 49855269
- Full Text :
- https://doi.org/10.1016/j.cbi.2010.03.019