PMID- 10706726
OWN - NLM
STAT- MEDLINE
DCOM- 20000328
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 164
IP  - 6
DP  - 2000 Mar 15
TI  - Distinct T cell/renal tubular epithelial cell interactions define differential 
      chemokine production: implications for tubulointerstitial injury in chronic 
      glomerulonephritides.
PG  - 3323-9
AB  - Chemokines can promote interstitial fibrosis that is, in turn, a strong predictor 
      of renal failure in chronic glomerulonephritides (GN). Resident renal cells, 
      including renal tubular epithelial cells (RTEC), represent a prominent source of 
      chemokine expression. Evaluating those factors responsible for sustained 
      chemokine production by RTEC during GN is therefore crucial. The contribution of 
      interstitial T cells to such expression, and in particular the precise nature of 
      their interactions with RTEC, are poorly understood. Activated T cell/RTEC 
      coculture induced production of high levels of monocyte chemoattractant protein-1 
      (MCP-1), RANTES, and IFN-inducible protein-10 from RTEC. Using double-chamber 
      cultures and activated T cell plasma membrane preparations we demonstrated that 
      both cell contact and soluble factors contributed to RTEC chemokine production. 
      Importantly, different chemokines exhibited distinct activation requirements. 
      Thus, for RANTES cell contact was essential, but not sufficient. In contrast, 
      either soluble factors or cell contact induced MCP-1 and IFN-inducible protein-10 
      production, although both pathways were required for a maximal response. 
      Neutralization experiments identified critical roles in this process for 
      proinflammatory cytokines such as TNF-alpha, IL-1beta, and IFN-gamma as well as 
      membrane molecules such as LFA-1, CD40 ligand, and membrane bound TNF-alpha. 
      Finally, chemotactic bioassays of T cell/RTEC coculture supernatants demonstrated 
      80% reduction of monocyte migration following MCP-1 neutralization, indicating a 
      dominant role for this chemokine. In summary, activation of renal tubular cells 
      by infiltrating T cells can amplify and perpetuate local inflammatory responses 
      through chemokine production differentially mediated by soluble and cell 
      contact-dependent factors. Recognition of this regulatory diversity has important 
      implications in the choice of potential therapeutic targets in GN.
FAU - Kuroiwa, T
AU  - Kuroiwa T
AD  - Arthritis and Rheumatism Branch, National Institute of Arthritis and 
      Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 
      20892, USA. kuroiwat@arb.niams.nih.gov
FAU - Schlimgen, R
AU  - Schlimgen R
FAU - Illei, G G
AU  - Illei GG
FAU - McInnes, I B
AU  - McInnes IB
FAU - Boumpas, D T
AU  - Boumpas DT
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD40 Antigens/physiology
MH  - CD40 Ligand
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Communication/*immunology
MH  - Cell Membrane/immunology/metabolism/physiology
MH  - Cell Movement/immunology
MH  - Chemokine CCL2/physiology
MH  - Chemokines/*biosynthesis
MH  - Chronic Disease
MH  - Cytokines/metabolism/physiology
MH  - Epithelial Cells/*immunology/metabolism/pathology
MH  - Glomerulonephritis/*immunology/metabolism/pathology
MH  - Humans
MH  - Kidney Tubules/*immunology/*metabolism/pathology
MH  - Ligands
MH  - Lymphocyte Activation
MH  - Membrane Glycoproteins/physiology
MH  - Monocytes/immunology
MH  - Nephritis, Interstitial/*immunology/metabolism/pathology
MH  - Protein Binding/immunology
MH  - Solubility
MH  - T-Lymphocytes/immunology/*metabolism
EDAT- 2000/03/08 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/03/08 09:00
PHST- 2000/03/08 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/03/08 09:00 [entrez]
AID - ji_v164n6p3323 [pii]
AID - 10.4049/jimmunol.164.6.3323 [doi]
PST - ppublish
SO  - J Immunol. 2000 Mar 15;164(6):3323-9. doi: 10.4049/jimmunol.164.6.3323.