Interleukin-17 activates human renal epithelial cells in vitro and is expressed during renal allograft rejection.
Local production of cytokines plays a critical role in the regulation of pathophysiologic processes leading to rejection of transplanted organs. In the present study, the possible role of interleukin-17 (IL-17), a recently identified cytokine with unique properties, was investigated. IL-17 is specifically produced by activated T cells, whereas biological activities are restricted to the activation of nonhematopoietic cells. In vitro, IL-17 induced primary human proximal tubular epithelial cells, a type of cell regulating local interstitial inflammatory responses, to secrete higher levels of IL-6, IL-8, and monocyte chemoattractant protein-1, but not of the chemokine RANTES. The effect was specific for IL-17, because it was completely abrogated by a neutralizing anti-IL-17 antibody and was demonstrated to be dose- and time-dependent. In addition, IL-17 increased the production of complement component C3 by human proximal tubular epithelial cells, but not of other complement components. Immunofluorescence showed expression of IL-17 in kidney biopsies from patients suffering from graft rejection (8 of 8 positive), whereas pretransplant biopsies and normal kidneys were negative (0 of 6). Analysis of whole kidney isolates confirmed the presence of IL-17 mRNA by reverse transcription-PCR. IL-17 expression could also be found in in vitro cultured and activated graft-infiltrating T cells. These results represent the first demonstration of IL-17 protein expression in pathologic conditions and suggest that IL-17 might be important in the regulation of local inflammatory responses.
Department of Nephrology, Leiden University Hospital, The Netherlands.
C
C
Van Kooten
J G
JG
Boonstra
M E
ME
Paape
F
F
Fossiez
J
J
Banchereau
S
S
Lebecque
J A
JA
Bruijn
J W
JW
De Fijter
L A
LA
Van Es
M R
MR
Daha
D001483:Base Sequence; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003176:Complement C3 / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology; D015870:Gene Expression; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000276:immunology*; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D018932:Chemokine CCL2; D003176:Complement C3; D017931:DNA Primers; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger