Caffeic acid phenethyl ester modifies the Th1/Th2 balance in ileal mucosa after gamma-irradiation in the rat by modulating the cytokine pattern.
OBJECTIVE
To pharmacologically modulate Th polarization in the ileum exposed to ionizing radiation by using the immuno-modulatory/apoptotic properties of Caffeic Acid Phenethyl Ester (CAPE).


METHODS
Rats received CAPE (30 mg/kg) treatment ip 15 min prior to intestinal 10 Gy gamma-irradiation and once a day for a 6 d period after irradiation. Expression of genes implicated in Th differentiation in ileal mucosa (IL-23/IL-12Rbeta2), Th cytokine responses (IFN-gamma, IL-2, IL-4, IL-13), Th migratory behaviour (CXCR3, CCR5, CCR4), Th signalling suppressors (SOCS1, SOCS3), transcription factor (T-Bet, GATA-3) and apoptosis (FasL/Fas, TNF/TNFR, XIAP, Bax, caspase-3) was analyzed by RT-PCR 6 h and 7 d post-irradiation. CD4(+) and TUNEL positive cells were visualized by immunostaining.


RESULTS
The expression of Th1-related cytokine/chemokine receptors (IFN-gamma, IL-2, CXCR3, CCR5) was repressed at 7 d post-irradiation while Th2 cell cytokine/chemokines (IL-4, IL-13, CCR4) were not repressed or even upregulated. The irradiation-induced Th2 profile was confirmed by the upregulation of both Th2-specific transcription factor GATA-3 and SOCS3. Although an apoptosis event occurred 6 h after 10 Gy of intestinal gamma-irradiation, apoptotic mediator analysis showed a tendency to apoptotic resistance 7 d post-irradiation. CAPE amplified apoptotic events at 6 h and normalized Bax/FasL expressions at 7 d.


CONCLUSIONS
CAPE prevented the ileal Th2 immune response by modulating the irradiation-influenced cytokine environment and apoptosis.
Grémy
Olivier
O
Institute for Radioprotection and Nuclear Safety, IRSN, BP no. 17, F-92262 Fontenay-aux-Roses Cedex, France.
Benderitter
Marc
M
Linard
Christine
C
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005720:Gamma Rays; D007082:Ileum / Q000187:drug effects* / Q000528:radiation effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018417:Th1 Cells / Q000187:drug effects* / Q000528:radiation effects*; D018418:Th2 Cells / Q000187:drug effects* / Q000528:radiation effects*; D013997:Time Factors
D002109:Caffeic Acids; D016207:Cytokines; D053148:Caspase 3; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol