Interleukin-1B and 6-Induced Calcium Channel Current Modulation in MC3T3-E1 Osteoblast Cell Line

Interleukin-1B (IL-1B) and -6 (IL-6) are inflammatory cytokines that are involved in bone resorption under pathological conditions. The cytokines are also involved in bone remodeling under physiological conditions. Voltage sensitive Ca2+ channels (VSCCs) serve as crucial mediators of membrane excitability and many Ca2+-dependent functions such as growth of bone, regulate proliferation, differentiation, enzyme activity and gene expression. The effects of IL-1B and -6 on VSCCs in osteoblast cell line (MC3T3-E1) were investigated using patch-clamp recording. Our results showed that application of 50 pM-50 nM IL-1B facilitated VSCCs current (ICa) carried by Ba2+ (IBa). Application of 50 pM-5 nM IL-6 facilitated IBa. In contrast, 50 nM IL-6 inhibited IBa in MC3T3-E1 cells. Treatment with MAPK inhibitor, PD98059, attenuated the 5 nM IL-6-induced facilitation of IBa. Treatment with STAT3 inhibitor, staffic, attenuated the 50 nM IL-6-induced inhibition of IBa. Treatment with PD98059 also attenuated the 50 nM IL-6-induced inhibition of IBa. These results suggest that 5 nM IL-6 facilitates VDCCs involving MAPK pathways. In addition, 50 nM IL-6 inhibits VDCCs involving STAT3 and MAPK pathways in MC3T3-E1 cells.