TWEAK-induced RANTES production by MC3T3-E1 cells involves the PI3K-Akt pathway. (a) MC3T3-E1 cells were cultured in the presence or absence of 100 ng/ml TWEAK with or without 10 μM LY294002, 10 μM PD98059, or 3 μM Helenalin for 48 hours. The culture supernatants were then collected, and the RANTES concentrations were measured by enzyme-linked immunosorbent assay. (b) MC3T3-E1 cells were stimulated with 100 ng/ml TWEAK for the indicated time periods. The cell lysates were then subjected to immunoblotting with antibody specific for phosphorylated Akt, Akt, phosphorylated Erk p42/44, and Erk p42/44. Values represent the mean ± standard deviation. *p < 0.05 compared with corresponding control. Similar results were obtained in at least three independent experiments. RANTES, regulated upon activation, healthy T cell expressed and secreted; TWEAK, tumour necrosis factor-like weak inducer of apoptosis.