CD137 Regulates NFATc1 Expression in Mouse VSMCs through TRAF6NF-κB p65 Signaling Pathway

Abstract EN

Our previous study proved that CD137-CD137L interaction can regulate the expression of NFATc1.

Here, we investigated whether CD137 signaling regulates the expression of NFATc1 in mice VSMCs through TRAF6/NF-κB p65 pathway.

Data shows that the CD137 expression can be stimulated by TNF-α in a time-dependent manner in mouse VSMCs.

Knockdown of TRAF6 by siTRAF6 significantly attenuated agonist-CD137mAb induced increase of NF-κB p65 and NFATc1 in VSMCs.

Pretreatment with a NF-κB inhibitor PDTC for 30 min inhibited the expression of p-p65 in both cytoplasm and nucleus in VSMCs.

Thus, the protein level of NFATc1 can be suppressed through inhibition of p-p65.

Finally, we also show that the levels of IL-2 and IL-6 can be increased by agonist-CD137 stimulation and decreased when NFATc1 was suppressed.

Our data suggest that activated CD137 signaling regulates the expression of NFATc1 and its downstream factors through TRAF6/NF-κB p65 pathways in VSMCs.

These findings provide a novel target for treatment of atherosclerosis.