TY - JOUR
T1 - Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes
AU - Chiocchetti, Annalisa
AU - Miglio, Gianluca
AU - Mesturini, Riccardo
AU - Varsaldi, Federica
AU - Mocellin, Marco
AU - Orilieri, Elisabetta
AU - Dianzani, Chiara
AU - Fantozzi, Roberto
AU - Dianzani, Umberto
AU - Lombardi, Grazia
PY - 2006/7/22
Y1 - 2006/7/22
N2 - 1. The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml -1 phytohemagglutinin plus 2 U ml -1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml -1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). 2. L-Glutamate (1 × 10 -8-1 × 10 -4 M) significantly (P≤0.01) inhibited AICD in a concentration-dependent manner (EC 50=6.3 × 10 -8 M; maximum inhibition 54.8±6.3% at 1 × 10 -6 M). 3. The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC 50 values were: 3.2 × 10 -7 M for (1S,3R)-ACPD; 4.5 × 10 -8 M for quisqualate; 1.0 × 10 -6 M for (S)-3,5-DHPG; 2.0 × 10 -5 M for CHPG. 4. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10 -6 M. The IC 50 values calculated were: 8.7 × 10 -5, 4.3 × 10 -6 and 6.3 × 10 -7 M for AIDA, LY 367385 and MPEP, respectively. 5. L-Glutamate (1 × 10 -6 M; 18 h) significantly (P≤0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. 6. Expression of both mGlu 1 and mGlu 5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase-PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. 7. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms.
AB - 1. The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml -1 phytohemagglutinin plus 2 U ml -1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml -1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). 2. L-Glutamate (1 × 10 -8-1 × 10 -4 M) significantly (P≤0.01) inhibited AICD in a concentration-dependent manner (EC 50=6.3 × 10 -8 M; maximum inhibition 54.8±6.3% at 1 × 10 -6 M). 3. The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC 50 values were: 3.2 × 10 -7 M for (1S,3R)-ACPD; 4.5 × 10 -8 M for quisqualate; 1.0 × 10 -6 M for (S)-3,5-DHPG; 2.0 × 10 -5 M for CHPG. 4. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10 -6 M. The IC 50 values calculated were: 8.7 × 10 -5, 4.3 × 10 -6 and 6.3 × 10 -7 M for AIDA, LY 367385 and MPEP, respectively. 5. L-Glutamate (1 × 10 -6 M; 18 h) significantly (P≤0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. 6. Expression of both mGlu 1 and mGlu 5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase-PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. 7. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms.
KW - Apoptosis
KW - Cell death
KW - Fas/FasL system
KW - Human T lymphocytes
KW - L-Glutamate
KW - Metabotropic glutamate receptors
UR - http://www.scopus.com/inward/record.url?scp=33746069308&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0706746
DO - 10.1038/sj.bjp.0706746
M3 - Article
SN - 0007-1188
VL - 148
SP - 760
EP - 768
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -