PMID- 12208776
OWN - NLM
STAT- MEDLINE
DCOM- 20030220
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 137
IP  - 2
DP  - 2002 Sep
TI  - Production of inflammatory mediators by renal epithelial cells is insensitive to 
      glucocorticoids.
PG  - 197-204
AB  - 1. In the present study we investigated the effect of glucocorticoids on the 
      activation of renal tubular epithelial cells, which are thought to play an 
      important role in inflammatory processes in the kidney. 2. Activation of renal 
      epithelial cells by IL-1, TNF-alpha or CD40L resulted in increased production of 
      cytokines and chemokines. Both in the renal epithelial cell line HK-2 and in 
      primary cultures of human proximal tubular epithelial cells (PTEC) production of 
      IL-6, IL-8 and monocyte chemotactic protein 1 (MCP-1) was not inhibited by 
      glucocorticoids, independent of the stimulus. 3. In contrast, dexamethasone 
      strongly inhibited cytokine production by immortalized renal fibroblasts and an 
      airway epithelial cell line (A549). 4. Stimulation of renal epithelial cells 
      resulted in activation of NF-kappaB, a pivotal transcription factor in the 
      regulation of cytokine genes, as was shown by IkappaB-alpha degradation and 
      increased DNA-binding activity. In contrast to dexamethasone, addition of the 
      NF-kappaB inhibitors pyrrolidine dithiocarbamate (PDTC) and 
      n-tosyl-l-phenylalanine chloromethyl ketone (TPCK) completely abolished cytokine 
      and chemokine production. 5. Renal epithelial cells express abundant levels of 
      the functional glucocorticoid receptor alpha (GRalpha) isoform and low levels of 
      the inhibitory beta isoform (GRbeta). 6. In conclusion, cytokine production by 
      renal epithelial cells is insensitive to the inhibitory effects of 
      glucocorticoids. The lack of dexamethasone-mediated inhibition was specific for 
      renal epithelial cells and could not be explained by an increased expression of 
      the glucocorticoid receptor beta isoform.
FAU - de Haij, Simone
AU  - de Haij S
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Woltman, Andrea M
AU  - Woltman AM
FAU - Bakker, Astrid C
AU  - Bakker AC
FAU - Daha, Mohamed R
AU  - Daha MR
FAU - van Kooten, Cees
AU  - van Kooten C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (glucocorticoid receptor alpha)
RN  - 0 (glucocorticoid receptor beta)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Cells, Cultured
MH  - Dexamethasone/*pharmacology
MH  - Epithelial Cells/drug effects/metabolism
MH  - Humans
MH  - Interleukin-1/pharmacology
MH  - Interleukin-6/*biosynthesis
MH  - Kidney Tubules, Proximal/cytology/*drug effects/metabolism
MH  - NF-kappa B/physiology
MH  - RNA, Messenger/analysis
MH  - Receptors, Glucocorticoid/analysis/genetics
MH  - Tumor Necrosis Factor-alpha/pharmacology
PMC - PMC1573489
EDAT- 2002/09/05 10:00
MHDA- 2003/02/21 04:00
PMCR- 2003/09/01
CRDT- 2002/09/05 10:00
PHST- 2002/09/05 10:00 [pubmed]
PHST- 2003/02/21 04:00 [medline]
PHST- 2002/09/05 10:00 [entrez]
PHST- 2003/09/01 00:00 [pmc-release]
AID - 0704866 [pii]
AID - 10.1038/sj.bjp.0704866 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2002 Sep;137(2):197-204. doi: 10.1038/sj.bjp.0704866.