Expression of the IL-2 receptor on human renal proximal tubular epithelial cells.
The high-affinity receptor for interleukin (IL)-2, IL-2R, is composed of three chains, i.e., the alpha, beta, and gamma chains. Previous studies have shown that human proximal tubular epithelial cells (PTEC) express IL-2R alpha during inflammation, such as in the kidneys after renal transplantation or in crescentic glomerulonephritis. Furthermore, in this study it is shown that PTEC in culture produce more complement C3 after stimulation with IL-2, suggesting the presence of a functional IL-2R on PTEC. In these experiments, the binding of IL-2 to PTEC was analyzed. PTEC stimulated with IL-2 exhibited very low binding of digoxigenin-labeled IL-2; however, stimulation of PTEC with IL-2, in combination with interferon (IFN)-gamma, resulted in increased binding of the digoxigenin-labeled IL-2. In addition, it was found that IL-2, together with IFN-gamma, enhanced the production of C3 by PTEC from baseline levels of 69.6 +/- 3.4 to 198.6 +/- 3.3 ng of C3 per 10(6) cells. The surface expression of IL-2R alpha and IL-2Rbeta was analyzed using monoclonal antibodies. Although unstimulated PTEC hardly showed detectable expression of these chains, stimulation of PTEC with the combination of IL-2 and IFN-gamma resulted in increases of the index of mean fluorescence for the alpha- and beta-chains of 5.5 +/- 0.5 and 9.7 +/- 0.7, respectively. Reverse transcription-PCR analysis revealed mRNA expression not only for the alpha- and beta-chains, but also for the gamma-chain, after stimulation with the combination of IL-2 and IFN-gamma. This study demonstrates that PTEC express the high-affinity IL-2R and that the IL-2R might be involved in the regulation of production of complement component C3 found during renal inflammation.
Gerritsma
J S
JS
Department of Nephrology, Leiden University Hospital, The Netherlands.
Gerritsen
A F
AF
van Kooten
C
C
van Es
L A
LA
Daha
M R
MR
D001483:Base Sequence; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*
D003176:Complement C3; D017931:DNA Primers; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma