PMID- 11592942
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20211203
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 281
IP  - 5
DP  - 2001 Nov
TI  - Complement C5b-9 induces cyclooxygenase-2 gene transcription in glomerular 
      epithelial cells.
PG  - F841-50
AB  - In rat membranous nephropathy, complement C5b-9 induces glomerular epithelial 
      cell (GEC) injury and proteinuria, which is partially mediated by eicosanoids. 
      Rat GEC in culture express cyclooxygenase (COX)-1 constitutively, whereas COX-2 
      expression is induced by C5b-9. Both isoforms contribute to complement-induced 
      prostaglandin generation. The present study addresses mechanisms of 
      complement-induced COX-2 expression in GEC. Downregulation of protein kinase C 
      (PKC) blunted complement-induced upregulation of COX-2 mRNA. Complement and 
      phorbol 12-myristate 13-acetate (PMA) both stimulated COX-2 promoter activity. 
      C5b-9 activated c-Jun NH(2)-terminal kinase (JNK), and inhibition of JNK activity 
      by transfection of a kinase-inactive JNK1 partially inhibited complement-induced 
      (but not PMA-induced) COX-2 promoter activation. Conversely, a constitutively 
      active mitogen-activated protein or extracellular signal-regulated kinase kinase 
      kinase (MEKK)-1, a kinase upstream of JNK, increased COX-2 promoter activity. 
      MEKK-induced COX-2 promoter activation was not affected by downregulation of PKC 
      and was augmented by PMA. Thus, in GEC, PKC and JNK pathways contribute 
      independently to complement-induced COX-2 expression. Nuclear factor-kappaB was 
      also activated by complement in GEC but did not contribute to complement-induced 
      COX-2 upregulation.
FAU - Takano, T
AU  - Takano T
AD  - Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada 
      H3A 2B4. ttomok@po-box.mcgill.ca
FAU - Cybulsky, A V
AU  - Cybulsky AV
FAU - Yang, X
AU  - Yang X
FAU - Aoudjit, L
AU  - Aoudjit L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Complement Membrane Attack Complex)
RN  - 0 (Isoenzymes)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (Map3k1 protein, mouse)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Complement Membrane Attack Complex/*pharmacology
MH  - Cyclooxygenase 2
MH  - Enzyme Activation/drug effects
MH  - Epithelial Cells/enzymology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Isoenzymes/*genetics
MH  - *JNK Mitogen-Activated Protein Kinases
MH  - Kidney Glomerulus/*enzymology
MH  - MAP Kinase Kinase 4
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - NF-kappa B/physiology
MH  - Promoter Regions, Genetic
MH  - Prostaglandin-Endoperoxide Synthases/*genetics
MH  - Protein Kinase C/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - RNA, Messenger/analysis
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
EDAT- 2001/10/11 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/11 10:00
PHST- 2001/10/11 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/11 10:00 [entrez]
AID - 10.1152/ajprenal.2001.281.5.F841 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2001 Nov;281(5):F841-50. doi: 
      10.1152/ajprenal.2001.281.5.F841.