We previously reported that jellyfish collagen stimulates both the acquired and 
innate immune responses. In the acquired immune response, jellyfish collagen 
enhanced immunoglobulin production by lymphocytes in vitro and in vivo. 
Meanwhile, in the innate immune response jellyfish collagen promoted cytokine 
production and phagocytotic activity of macrophages. The facts that jellyfish 
collagen plays several potential roles in stimulating cytokine production by 
macrophages have further attracted us to uncover its mechanisms. We herein 
describe that the cytokine production-stimulating activity of jellyfish collagen 
was canceled by a Toll-like receptor 4 (TLR4) inhibitor. Moreover, jellyfish 
collagen stimulated phosphorylation of inhibitor of κBα (IκBα), promoted the 
translocation of nucleus factor-κB (NF-κB), and activated c-Jun N-terminal 
kinase (JNK). A JNK inhibitor also abrogated the cytokine production-stimulating 
activity of jellyfish collagen. These results suggest that jellyfish collagen 
may facilitate cytokine production by macrophages through activation of NF-κB 
and JNK via the TLR4 signaling pathways.