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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Leukoc+Biol
2015 ; 97
(4
): 677-88
Nephropedia Template TP
J Leukoc Biol
2015[Apr]; 97
(4
): 677-88
PMID25713087
show ga
MDSCs are potent immunosuppressive cells that are induced during inflammatory
responses, as well as by cancers, to evade the anti-tumor immunity. We recently
demonstrated that marijuana cannabinoids are potent inducers of MDSCs. In the
current study, we investigated the epigenetic mechanisms through which THC, an
exogenous cannabinoid, induces MDSCs and compared such MDSCs with the naïve MDSCs
found in BM of BL6 (WT) mice. Administration of THC into WT mice caused increased
methylation at the promoter region of DNMT3a and DNMT3b in THC-induced MDSCs,
which correlated with reduced expression of DNMT3a and DNMT3b. Furthermore,
promoter region methylation was decreased at Arg1 and STAT3 in THC-induced MDSCs,
and consequently, such MDSCs expressed higher levels of Arg1 and STAT3. In
addition, THC-induced MDSCs secreted elevated levels of S100A8, a calcium-binding
protein associated with accumulation of MDSCs in cancer models. Neutralization of
S100A8 by use of anti-S100A8 (8H150) in vivo reduced the ability of THC to
trigger MDSCs. Interestingly, the elevated S100A8 expression also promoted the
suppressive function of MDSCs. Together, the current study demonstrates that THC
mediates epigenetic changes to promote MDSC differentiation and function and that
S100A8 plays a critical role in this process.
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