PMID- 17314328
OWN - NLM
STAT- MEDLINE
DCOM- 20070531
LR  - 20220129
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 18
IP  - 4
DP  - 2007 Apr
TI  - Inhibition of p38 mitogen-activated protein kinase is effective in the treatment 
      of experimental crescentic glomerulonephritis and suppresses monocyte 
      chemoattractant protein-1 but not IL-1beta or IL-6.
PG  - 1167-79
AB  - Activation of p38 mitogen-activated protein kinase (MAPK) is known to be 
      important in cytokine production and cell survival in inflammation. This study 
      examined the effect of inhibiting p38 MAPK after onset of renal injury in an 
      experimental model of crescentic glomerulonephritis. Furthermore, this study 
      investigated whether p38 MAPK inhibition would cause widespread suppression of 
      the cytokine network in vivo or uncontrolled apoptosis. In the in vivo studies, 
      daily treatment with a p38 MAPKalpha/beta inhibitor was started 1 h (early 
      treatment study) or 4 d (late treatment study) after induction of nephrotoxic 
      nephritis in Wistar Kyoto rats. The treated rats remained healthy with normal 
      weight gain during the study. Both early and late treatment with p38 MAPK 
      inhibitor reduced renal monocyte chemoattractant protein-1 (MCP-1) levels, the 
      number of glomerular macrophages, the severity of tissue injury, and proteinuria 
      compared with the vehicle group. Unexpected, treatment with p38 MAPK inhibitor 
      did not suppress renal levels of IL-1beta or IL-6. In the in vitro study, the p38 
      MAPKalpha/beta inhibitor reduced production of MCP-1 and IL-6 by TNF-alpha-or 
      IL-1beta-stimulated mesangial cells without any effect on cell viability or 
      apoptosis. In conclusion, p38 MAPK inhibition is effective in reducing the 
      severity of crescentic glomerulonephritis even when treatment is started after 
      onset of disease. The therapeutic effect is associated with selective suppression 
      of MCP-1, without widespread suppression of cytokine production or increased 
      apoptosis. Therefore, p38 MAPK therapeutic blockade is a promising strategy in 
      the treatment of antibody-mediated glomerulonephritis.
FAU - Sheryanna, Abdulmunem
AU  - Sheryanna A
AD  - Renal Section, Division of Medicine, Imperial College London, Hammersmith 
      Hospital Campus, Du Cane Road, London W12 ONN, UK.
FAU - Bhangal, Gurjeet
AU  - Bhangal G
FAU - McDaid, John
AU  - McDaid J
FAU - Smith, Jennifer
AU  - Smith J
FAU - Manning, Anthony
AU  - Manning A
FAU - Foxwell, Brian M J
AU  - Foxwell BM
FAU - Feldmann, Marc
AU  - Feldmann M
FAU - Cook, H Terence
AU  - Cook HT
FAU - Pusey, Charles D
AU  - Pusey CD
FAU - Tam, Frederick W K
AU  - Tam FW
LA  - eng
GR  - G0400443/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070221
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/analysis/*antagonists & inhibitors
MH  - Glomerulonephritis/*drug therapy/immunology/pathology
MH  - Intercellular Adhesion Molecule-1/analysis
MH  - Interleukin-1beta/analysis/*antagonists & inhibitors
MH  - Interleukin-6/analysis/*antagonists & inhibitors
MH  - Male
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Rats
MH  - Rats, Inbred WKY
MH  - p38 Mitogen-Activated Protein Kinases/*antagonists & inhibitors
EDAT- 2007/02/23 09:00
MHDA- 2007/06/01 09:00
CRDT- 2007/02/23 09:00
PHST- 2007/02/23 09:00 [pubmed]
PHST- 2007/06/01 09:00 [medline]
PHST- 2007/02/23 09:00 [entrez]
AID - ASN.2006010050 [pii]
AID - 10.1681/ASN.2006010050 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2007 Apr;18(4):1167-79. doi: 10.1681/ASN.2006010050. Epub 2007 
      Feb 21.