PMID- 12039983
OWN - NLM
STAT- MEDLINE
DCOM- 20021104
LR  - 20220409
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 13
IP  - 6
DP  - 2002 Jun
TI  - MCP-1 induces inflammatory activation of human tubular epithelial cells: 
      involvement of the transcription factors, nuclear factor-kappaB and activating 
      protein-1.
PG  - 1534-47
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine synthesized by 
      several cell types, e.g., inflammatory cells, such as monocytes, and resident 
      renal cells, such as human tubular epithelial cells (TECs). Besides induction of 
      monocyte recruitment, MCP-1 has been suggested to induce non-leukocytes to 
      produce cytokines and adhesion molecules. Inflammation of the tubulointerstitium 
      is a hallmark of many renal diseases and contributes to progression of renal 
      failure; the purpose therefore of this study was to investigate the influence of 
      MCP-1 on markers of inflammatory activation in human TECs. MCP-1 stimulated 
      interleukin-6 (IL-6) secretion and intercellular adhesion molecule-1 (ICAM-1) 
      synthesis in a time- and dose-dependent manner. In parallel, MCP-1 increased IL-6 
      and ICAM-1 mRNA expression in human TECs. Pretreatment with pertussis toxin, 
      GF109203X, BAPTA-AM, and pyrrolidine dithiocarbamate inhibited MCP-1-dependent 
      IL-6 and ICAM-1 synthesis, suggesting the involvement of Gi-proteins, protein 
      kinase C, intracellular Ca(2+), and nuclear factor-kappaB (NF-kappaB) in MCP-1 
      signaling. Using electrophoretic gel mobility shift assay, we observed that MCP-1 
      stimulated binding activity of NF-kappaB. Binding activity of the activator 
      protein-1 (AP-1), which has been implicated to regulate induction of the IL-6 
      gene together with NF-kappaB, was also stimulated by MCP-1. In the present 
      experiments, NF-kappaB and AP-1 were involved in the MCP-1-mediated induction of 
      IL-6, as demonstrated by cis element double-stranded (decoy) oligonucleotides 
      (ODN). In contrast to IL-6 release, MCP-1-induced ICAM-1 expression was 
      predominantly dependent on NF-kappaB activation. These results document for the 
      first time that MCP-1 induces an inflammatory response in human TECs. This may be 
      an important new mechanism in the pathogenesis of tubulointerstitial 
      inflammation.
FAU - Viedt, Christiane
AU  - Viedt C
AD  - Department of Internal Medicine, Division of Cardiology, Ruperto Carola 
      University, Heidelberg, Germany.
FAU - Dechend, Ralph
AU  - Dechend R
FAU - Fei, Jianwei
AU  - Fei J
FAU - Hansch, Gertrud M
AU  - Hansch GM
FAU - Kreuzer, Jorg
AU  - Kreuzer J
FAU - Orth, Stephan R
AU  - Orth SR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Transcription Factor AP-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism/*pharmacology
MH  - Epithelial Cells/drug effects/immunology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/biosynthesis
MH  - Interleukin-6/biosynthesis/genetics
MH  - Kidney Tubules/*drug effects/immunology
MH  - NF-kappa B/*physiology
MH  - Nephritis/*etiology
MH  - RNA, Messenger/analysis
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/genetics
MH  - Transcription Factor AP-1/*physiology
EDAT- 2002/06/01 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - 10.1097/01.asn.0000015609.31253.7f [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2002 Jun;13(6):1534-47. doi: 
      10.1097/01.asn.0000015609.31253.7f.