PMID- 11053480
OWN - NLM
STAT- MEDLINE
DCOM- 20001130
LR  - 20210511
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 11
IP  - 11
DP  - 2000 Nov
TI  - Interleukin-17 and CD40-ligand synergistically enhance cytokine and chemokine 
      production by renal epithelial cells.
PG  - 2044-2055
LID - 10.1681/ASN.V11112044 [doi]
AB  - Renal allograft rejection is characterized by an influx of inflammatory cells. 
      Interaction between infiltrating T cells and resident parenchymal cells might 
      play an important role in the ongoing inflammatory response. The present study 
      demonstrates that CD40L, a product of activated T cells, is locally expressed in 
      kidneys undergoing rejection. Furthermore, during rejection, CD40 expression not 
      only is present on most graft infiltrating cells but also is increased on 
      resident tubular epithelial cells (TEC). To obtain more detailed insight in the 
      consequences of T cell/TEC interaction, we analyzed the production of chemokines, 
      including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and 
      regulated upon activation, normal T cell expressed and secreted (RANTES), and the 
      production of IL-6 by cultured human primary TEC in response to activation with 
      CD40L in vitro. In addition, we studied the interaction with IL-17, a 
      T-cell-specific cytokine previously demonstrated to be present during renal 
      allograft rejection. The results, obtained by enzyme-linked immunosorbent assay, 
      indicate that simultaneous activation of TEC with IL-17 and CD40L synergistically 
      enhances production of IL-6 (2.1-fold higher than sum of single stimulations) and 
      the chemokines IL-8 (15-fold) and RANTES (5.8-fold) as demonstrated by 
      statistical analysis (P: < 0.05), whereas effects on MCP-1 (1.4-fold) are 
      additive. Part of the synergy can be explained by increased CD40 expression on 
      TEC upon IL-17 stimulation. The synergy is not unique for TEC, because similar 
      responses were found with human synoviocytes and a foreskin fibroblast cell line 
      (FS4). Stimulation of TEC with CD40L results in activation of NF-kappaB and 
      induction of cytokine production by IL-17 and CD40L is prevented by addition of 
      the NF-kappaB inhibitor pyrrolidine dithiocarbamate. These data suggest an 
      important role for T cells in renal allograft rejection by acting on parenchymal 
      cells via both soluble mediators and direct cellular contact.
FAU - Woltman, Andrea M
AU  - Woltman AM
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - DE Haij, Simone
AU  - DE Haij S
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Boonstra, Joke G
AU  - Boonstra JG
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Gobin, Sam J P
AU  - Gobin SJP
AD  - Department of Immunohematology and Blood Bank, Leiden University Medical Center, 
      Leiden, The Netherlands.
FAU - Daha, Mohamed R
AU  - Daha MR
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Kooten, Cees VAN
AU  - Kooten CV
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
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 (CD40 Antigens)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (IL17RA protein, human)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-17)
RN  - 0 (Recombinant Proteins)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - CD40 Antigens/metabolism/pharmacology
MH  - CD40 Ligand/metabolism/*pharmacology
MH  - Cells, Cultured
MH  - Chemokines/*biosynthesis
MH  - Cytokines/*biosynthesis
MH  - Drug Synergism
MH  - Epithelial Cells/drug effects/metabolism
MH  - Graft Rejection/metabolism
MH  - Humans
MH  - Interleukin-17/*pharmacology
MH  - Interleukin-6/biosynthesis
MH  - Kidney/metabolism
MH  - Kidney Transplantation
MH  - Kidney Tubules/cytology/drug effects/*metabolism
MH  - NF-kappa B/physiology
MH  - Receptors, Interleukin/metabolism
MH  - Receptors, Interleukin-17
MH  - Recombinant Proteins/metabolism
EDAT- 2000/10/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/29 11:00
PHST- 2000/10/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/29 11:00 [entrez]
AID - 11/11/2044 [pii]
AID - 10.1681/ASN.V11112044 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2000 Nov;11(11):2044-2055. doi: 10.1681/ASN.V11112044.