Regulation of human interleukin 14 transcription in vitro and in vivo after renal transplantation.
BACKGROUND
Alloantibodies and B lymphocytes are felt to contribute in increasingly important ways to the pathogenesis of both acute and chronic allograft injury. The mechanisms that lead to the formation of posttransplant alloantibodies despite immunosuppressive therapy have not been fully elucidated. Interleukin 14 (IL-14) or high molecular weight B cell growth factor secreted by activated T and B cells and follicular dendritic cells promotes B cell growth, survival and memory, and antibody production. The potential role of IL-14 in human transplantation has not been examined.


METHODS
Using quantitative polymerase chain reaction techniques, we examined IL-14 mRNA transcript levels in human cells and compared them to IL-2. Interleukin-14 mRNA levels were measured in isolated human T cells stimulated in vitro with mitogen and alloantigen in the presence or absence of immunosuppressive drugs. In vivo, IL-14 transcript levels were measured in peripheral blood leukocytes isolated from patients after renal transplantation.


RESULTS
In vitro, both IL-14 and IL-2 transcript levels increase after alloantigen and mitogen stimulation and are suppressed by currently used immunosuppressive agents. In vivo, IL-14 and IL-2 behave differently as IL-14 transcript levels are not reduced by immunosuppressive therapy. Interleukin-14 transcripts also increase after both immune and nonimmune injury to renal allografts.


CONCLUSIONS
This is the first demonstration of human IL-14 mRNA regulation in vitro and in vivo. Given the important effects of IL-14 on B cell proliferation and antibody production, increases in IL-14 transcript levels may play a role in alloantibody formation after renal transplantation.
Leca
Nicolae
N
Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA, USA.
Laftavi
Mark
M
Shen
Long
L
Matteson
Kristin
K
Ambrus
Julian
J
Pankewycz
Oleh
O
D001402:B-Lymphocytes / Q000378:metabolism; D049109:Cell Proliferation; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007376:Interleukin-2 / Q000378:metabolism; D007518:Isoantibodies / Q000737:chemistry; D016030:Kidney Transplantation / Q000379:methods*; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D033921:Vesicular Transport Proteins / Q000096:biosynthesis* / Q000502:physiology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007518:Isoantibodies; D012333:RNA, Messenger; C488100:TXLNA protein, human; D033921:Vesicular Transport Proteins; D003907:Dexamethasone