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[Effect of extracellular-signal regulated kinase 1/2 specific repressor PD98059 on murine lymphocyte proliferation]
Zhen-ping Teng1, Fei-yue Xing, Tong Wang
1Center for Tissue Transplantation and Immunology, College of Life Science and Techology, Jinan University, Guangzhou 510632, China.
Aim:
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.
Conclusion:
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.
Insights
PD98059, an inhibitor of extracellular signal regulated kinase 1/2 (ERK1/2) signaling, significantly inhibits murine lymphocyte proliferation. This compound blocks lymphocyte cell cycle progression at S and G2/M phases, highlighting ERK1/2
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Lymphocyte proliferation is crucial for adaptive immunity.
- Extracellular signal regulated kinase 1/2 (ERK1/2) signaling pathways regulate cell growth and differentiation.
- Understanding the role of ERK1/2 in lymphocyte proliferation is key to developing immunomodulatory therapies.
Purpose of the Study:
- To investigate the impact of PD98059, a specific ERK1/2 inhibitor, on murine lymphocyte proliferation.
- To elucidate the effects of PD98059 on lymphocyte cell cycle progression.
Main Methods:
- Murine lymphocytes were isolated and stained with CFDA-SE.
- Cells were stimulated with polyclonal activators: concanavalin A (ConA) or phorbol 12,13-dibutyrate (PDB) plus ionomycin (Ion).
- Proliferation and cell cycle distribution were analyzed by flow cytometry (FCM).
Main Results:
- PD98059 demonstrated a dose-dependent inhibition of ConA-induced lymphocyte proliferation.
- The inhibitor caused a significant block in the S and G2/M phases of the cell cycle.
- Similar effects were observed with PDB plus ionomycin stimulation, with more distinct S and G2/M phase arrests.
Conclusions:
- PD98059 effectively inhibits murine lymphocyte proliferation.
- The ERK1/2 signaling pathway is critical for lymphocyte proliferation.
- Inhibition of ERK1/2 signaling arrests lymphocytes in the S and G2/M phases, impacting cell cycle progression.
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