[Roles of ceruloplasmin in silica-induced JNK/ERK/AP-1 cell signaling pathway change]

To investigate the roles of ceruloplasmin (Cp) in JNK/ERK/ AP-1 cell signaling pathway change in human embryonic lung fibroblasts (HELFs) induced by silica.

Cp stimulated HELFs in different time points (before 1 h, accompanied with or after 1 h of silica-adding). HELFs were divided into these groups: control group, silica(100 microg/ml for 24 h) group, Cp (30 microg/ml for 24 h) group and silica plus Cp (100 microg/ml silica plus 30 microg/ml Cp) group. DN-JNK cells and DN-ERK cells (cells were transfected with dominant negative mutant plasmid) contained these groups: control group, silica group, silica plus Cp group. MTT assay was used to detect the effects of Cp on silica-induced cell proliferation. Western blot assay was performed to detect the levels of JNK, ERK, c-Jun, c-Fos and their phosphorylated levels.

Cp promoted cell proliferation induced by silica when silica stimulated HELFs 1 h then adding to Cp. Cp significantly increased silica-induced the high levels of JNK, ERK and phosphorylated JNK (p-JNK), p-ERK, p-c-Jun and p-c-fos protein. After inhibition of JNK or ERK, silica-and-Cp-induced cell proliferation was markedly decreased. When suppressing JNK protein, the increased levels of p-JNK, p-c-Jun and p-c-fos protein was not observed. The high levels of p-ERK, p-c-Jun and p-c-fos protein were decreased when inhibiting ERK protein.

Cp could further strengthen silica-induced cell proliferation by JNK/c-Jun/c-Fos and ERK/c-Jun cell signaling pathway.