Abstract

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 (I_Ca) carried by Ba²⁺ (I_Ba). Application of 50 pM-5 nM IL-6 facilitated I_Ba. In contrast, 50 nM IL-6 inhibited I_Ba in MC3T3-E1 cells. Treatment with MAPK inhibitor, PD98059, attenuated the 5 nM IL-6-induced facilitation of I_Ba. Treatment with STAT3 inhibitor, staffic, attenuated the 50 nM IL-6-induced inhibition of I_Ba. Treatment with PD98059 also attenuated the 50 nM IL-6-induced inhibition of I_Ba. 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.

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