PMID- 10411678
OWN - NLM
STAT- MEDLINE
DCOM- 19990803
LR  - 20171116
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 1
DP  - 1999 Jul
TI  - Synergistic effect of interleukin-1 and CD40L on the activation of human renal 
      tubular epithelial cells.
PG  - 41-51
AB  - BACKGROUND: Renal tubular epithelial cells are a central cell type in 
      tubulointerstitial inflammation because they can produce inflammatory mediators 
      such as cytokines and chemokines. Several signals derived from either monocytes 
      or activated T cells have been reported to regulate the activation of tubular 
      epithelial cells. We studied this regulation in more detail by combined treatment 
      with CD40 ligand and the proinflammatory cytokine interleukin-1 (IL-1) in vitro. 
      METHODS: The regulation of cytokine and chemokine production was studied in 
      primary cultures of human proximal tubular epithelial cells (PTECs). PTECs were 
      activated by coculture with CD40L-transfected murine fibroblasts in combination 
      with recombinant human cytokines. The production of IL-6, IL-8, monocyte 
      chemoattractant protein-1 (MCP-1), and RANTES were measured by specific 
      enzyme-linked immunosorbent assay. RESULTS: The combined activation of PTECs with 
      CD40L and IL-1 resulted in strong synergistic effects on the production of IL-6, 
      IL-8, and RANTES, whereas only an additive stimulation of MCP-1 production was 
      observed. The effects were specific for IL-1 and could be neutralized by the 
      addition of the IL-1R antagonist. Both IL-1alpha and IL-1beta showed similar 
      effects on cytokine production by PTECs. The effects of IL-1 were dose dependent, 
      and kinetic experiments showed that synergistic effects were observed after 24 
      hours of activation and remained present for at least five days. Reverse 
      transcription-polymerase chain reaction analysis showed that human PTECs could 
      express both IL-1alpha and IL-1beta. The activation of PTECs with IL-1 resulted 
      in an up-regulation of CD40 expression on these cells. CONCLUSIONS: A complex 
      network of regulation exists for the production of cytokines and chemokines by 
      PTECs. The combined treatment results in strong synergistic effects on IL-6, 
      IL-8, and RANTES production. This strengthens the potential role of tubular 
      epithelial cells in inflammatory responses within the kidney.
FAU - van Kooten, C
AU  - van Kooten C
AD  - Department of Nephrology, Leiden University, The Netherlands. 
      Kooten@Rullf2.Medfac.LeidenUniv.nl
FAU - van der Linde, X
AU  - van der Linde X
FAU - Woltman, A M
AU  - Woltman AM
FAU - van Es, L A
AU  - van Es LA
FAU - Daha, M R
AU  - Daha MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Interleukin-1)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Animals
MH  - CD40 Antigens/metabolism
MH  - CD40 Ligand
MH  - Cell Line
MH  - Chemokines/biosynthesis
MH  - Cytokines/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Epithelial Cells/drug effects/metabolism/physiology
MH  - Humans
MH  - Interleukin-1/metabolism/*pharmacology
MH  - Interleukin-6/biosynthesis
MH  - Kidney Tubules/*drug effects/metabolism/*physiology
MH  - Membrane Glycoproteins/*pharmacology
MH  - Mice
MH  - Protein Isoforms/metabolism/pharmacology
MH  - Receptors, Interleukin-1/antagonists & inhibitors
MH  - Time Factors
EDAT- 1999/07/20 00:00
MHDA- 1999/07/20 00:01
CRDT- 1999/07/20 00:00
PHST- 1999/07/20 00:00 [pubmed]
PHST- 1999/07/20 00:01 [medline]
PHST- 1999/07/20 00:00 [entrez]
AID - S0085-2538(15)46261-1 [pii]
AID - 10.1046/j.1523-1755.1999.00514.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Jul;56(1):41-51. doi: 10.1046/j.1523-1755.1999.00514.x.