Title
|
|
|
|
NF-kappa B mediated IL-6 production by renal epithelial cells is regulated by C-Jun NH2-terminal kinase
| |
Author
|
|
|
|
| |
Abstract
|
|
|
|
Tubular epithelial cells (TEC) play an important role in tubulointerstitial inflammation, a hallmark of most renal diseases, via production of cytokines and chemokines. In this study, the role of mitogen-activated protein kinases (MAPK) in regulation of the proinflammatory cytokine IL-6 in cultured human TEC in response to the leukocyte-derived factors IL-1, TNF-alpha, IL-17, and CD40L was investigated. IL-6 production induced by IL-1, TNF-alpha, and IL-17 was specifically inhibited by the c-jun NH2-terminal kinase (JNK) inhibitor SP600125, but not by a selective inhibitor of p38 MAPK, and was moderately increased when the ERK1/2 pathway was inhibited. Also for CD40L stimulation, inhibition of JNK resulted in a pronounced inhibition of IL-6 production. Although stimulation of TEC induced activation of activator protein-1 (AP-1), the down-stream target of JNK, reporter assays demonstrated that mutation of the AP-1 binding site in the IL-6 promoter did not affect gene transcription. Furthermore, IL-1-induced transcriptional activation of the IL-6 promotor was repressed by SP600125 or by co-transfection of a dominant-negative expression plasmid of c-jun even in the absence of a functional AP-1 binding site. This suggests that IL-6 production by renal epithelial cells is regulated by JNK, via a mechanism, however, independent of the AP-1 binding site. The data rather suggest that the JNK pathway may interfere with other signaling pathways, involving NF-kappa B and possibly ERK. |
| |
Language
|
|
|
|
English
| |
Source (journal)
|
|
|
|
Journal of the American Society of Nephrology. - Baltimore, Md, 1990, currens
| |
Publication
|
|
|
|
Baltimore, Md
:
2005
| |
ISSN
|
|
|
|
1046-6673
| |
DOI
|
|
|
|
10.1681/ASN.2004090781
| |
Volume/pages
|
|
|
|
16
:6
(2005)
, p. 1603-1611
| |
ISI
|
|
|
|
000229393900011
| |
Full text (Publisher's DOI)
|
|
|
|
| |
|