[Effect of extracellular-signal regulated kinase 1/2 specific repressor PD98059 on murine lymphocyte proliferation].
OBJECTIVE
To investigate the effect of PD98059, a specific repressor of extracellular signal regulated kinase 1/2 (ERK1/2), on the proliferation of the murine lymphocytes.


METHODS
Lymphocytes were isolated from lymphoid nodes of BALB/c mouse. After stained with carboxy fluorescein diacetate, succinimidyl ester(CFDA-SE), the cells were stimulated with polyclonal activators, concanavalin(ConA) and phorbol 12,13-dibutyrate(PDB) plus ionomycin(Ion). The proliferation and cell-cycle of lymphocytes were analyzed using flow cytometry(FCM).


RESULTS
CFDA-SE staining showed that 5, 10, 20, 30 and 40 micromol/L PD98059 could significantly inhibit the proliferation of murine lymphocytes induced by ConA. The inhibitory effect was dose-dependent(r=0.985, P<0.01). The optimal concentration of 30 micromol/L PD98059 was selected and its inhibitory effect was significantly decreased with prolongation of time (P<0.01); but the inhibitory rate increased. Analysis of the cell cycle induced by ConA revealed that the cells was blocked into S and G2/M phases as the concentration of PD98059 increased. However, the cell number in sub-G0/G1 peak (apoptotic peak) had no significant change under the concentration range used. PD98059 had the similar effect on the cells treated with PDB plus Ion, but S and G2/M phases were more distinct.


CONCLUSIONS
PD98059 can inhibit the proliferation of the murine lymphocytes and blocked them into S and G2/M phases, indicating the activation of ERK1/2 signaling pathway plays an important role in the proliferation of lymphocytes.
Teng
Zhen-ping
ZP
Center for Tissue Transplantation and Immunology, College of Life Science and Techology, Jinan University, Guangzhou 510632, China.
Xing
Fei-yue
FY
Wang
Tong
T
Li
Li-ping
LP
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects
D005419:Flavonoids; D003208:Concanavalin A; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one