Locally derived cytokines and upregulation of MHC class II genes in allografts.
BACKGROUND
In vitro, various cytokines can modulate the level of expression of major histocompatibility complex (MHC) Class II antigens. Major histocompatibility complex Class II hyperexpression occurs in many immunologic disorders in vivo, but the cytokines that affect this are difficult to analyze because they are produced in small amounts, they act locally, and their mRNAs have short half-lives.


METHODS
We studied the expression of cytokines known to up-regulate MHC Class II genes in heart allografts in mice from B10.BR donors to B10.D2 recipients by reverse transcription of mRNA and polymerase chain reaction amplification. The I-Abeta(k) gene expression was also studied in the same fully MHC incompatible strain combination.


RESULTS
Messenger RNA for interferon (INF)-gamma, interleukin (IL)-4, and tumor necrosis factor (TNF)-alpha, known inducers of MHC Class II expression in vitro, could be detected in allografts either 24 hours before or simultaneously with massive induction of graft specific I-Abeta mRNA. Interleukin-6 mRNA could be detected as early as 1 day after grafting.


CONCLUSIONS
These data suggest that known cytokine up-regulators of MHC Class II genes, i.e., IFN-gamma, IL-4, and TNF-alpha may contribute to the upregulation of graft-specific MHC Class II antigens during an allograft reaction. Also, IL-6 expression in allografts may result from the stress of the grafting procedure, as it is evident very early after grafting.
Kittur
Dilip S
DS
Department of Surgery, SUNY Upstate Medical University, Syracuse, New York, USA. kitturd@upstate.edu
Wilasrusmee
Chumpon
C
Han
Wang-Fang
WF
Xu
Renkui
R
Burdick
James F
JF
Adler
William
W
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005802:Genes, MHC Class II / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D006824:Hybridization, Genetic; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014184:Transplantation, Homologous; D015854:Up-Regulation
D016207:Cytokines; D007371:Interferon-gamma