Epithelial-derived neutrophil-activating factor-78 production in human renal tubule epithelial cells and in renal allograft rejection.
Chemotactic cytokines, or chemokines, are likely mediators of inflammatory cell recruitment in renal allograft rejection. A recent addition to the C-X-C super gene family branch of chemokines is epithelial-derived neutrophil-activating factor-78 (ENA-78). ENA-78 is a 78-amino acid peptide with neutrophil-activating and chemotactic properties. This chemokine is unique in that it was originally isolated and cloned from an IL-1-stimulated human pulmonary epithelial cell line, A549. In this article, we investigated whether ENA-78 could be produced by human renal epithelial cells. We found that primary cultures of human renal cortical epithelial cells with tubular cell attributes could express significantly increased steady state levels of ENA-78 mRNA when stimulated with IL-1 beta (2.0 ng/ml). In addition, these cells also secreted significantly increased ENA-78 antigen compared with controls when stimulated with IL-1 beta (2.0 ng/ml). Other proinflammatory agonists, including TNF alpha, IFN gamma, and LPS failed to stimulate ENA-78 steady state mRNA or antigenic peptide production by renal cortical epithelial cells. In addition, biopsy tissue from acutely rejecting human renal allografts had higher copy number of ENA-78 mRNA compared with nonrejecting renal allograft controls using a quantitative reverse transcriptase polymerase chain reaction method with a mutant ENA-78 transcript. In the proinflammatory milieu of the rejecting renal allograft, IL-1 beta produced by host and donor mononuclear cells may drive ENA-78 production by allograft tubule cells, thus effecting leukocyte recruitment into the tubulointerstitial compartment.
Department of Pathology, University of Michigan, Ann Arbor 48109-0602.
R L
RL
Schmouder
R M
RM
Streiter
A
A
Walz
S L
SL
Kunkel
D001483:Base Sequence; D002478:Cells, Cultured; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D015342:DNA Probes; D006084:Graft Rejection / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000096:biosynthesis; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D014184:Transplantation, Homologous
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D015342:DNA Probes; D007375:Interleukin-1; D016209:Interleukin-8; D012333:RNA, Messenger