Jellyfish collagen stimulates production of TNF-α and IL-6 by J774.1 cells through activation of NF-κB and JNK via TLR4 signaling pathway.

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.

Mode of action of the immunostimulatory effect of collagen from jellyfish.

We have previously demonstrated that collagen from jellyfish simulated immunoglobulin and cytokine production by human-human hybridoma line HB4C5 cells and by human peripheral blood lymphocytes (hPBL). The mode of action of the collagen as an immunostimulatory factor was investigated. The expression levels of immunoglobulin mRNAs in HB4C5 cells, and those of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta in hPBL were up-regulated by jellyfish collagen. In addition, this collagen activated IgM production by transcription-suppressed HB4C5 cells that had been treated with actinomycin D. This collagen also enhanced IgM production by translation-suppressed HB4C5 cells that had been treated with sodium fluoride, but was ineffective in accelerating IgM production by HB4C5 cells treated with cycloheximide. Moreover, the intracellular IgM level in HB4C5 cells treated with the post-translation inhibitor, monensin, was increased by this collagen. These results suggest that collagen from jellyfish stimulated not only the transcription activity, but also the translation activity for enhanced immunoglobulin and cytokine production.

Protease-resistant fraction of smoked, dried bonito alleviates atopic dermatitis-like skin lesions in NC/Nga mice.

The effect of smoke-dried bonito undigested fraction remaining after microbial protease treatment (SDBR) on a spontaneously occurring mouse model of atopic dermatitis was studied in male 5-wk-old, NC/Nga mice. Smoke-dried bonito, Katsuobushi, is a traditional Japanese food. SDBR contains 2 major components: bonito oil and protease-undigested proteins. Mice were fed a casein diet containing corn oil (C diet) or a diet containing SDBR (SDBR diet) for 18 wk. In comparison with the C diet, the SDBR diet alleviated the increase in skin severity score and plasma IgE concentration in a time-dependent manner, and lowered leucotriene B(4) (LTB(4))-releasing ability upon calcium ionophore A23187 stimulation. The SDBR diet did not affect scratching time. These results demonstrate that SDBR diet alleviates atopic dermatitis-like skin lesions in NC/Nga mice.

Hypocholesterolemic effect of katsuobushi, smoke-dried bonito, prevents ovarian hormone deficiency-induced hypercholesterolemia.

The purpose of this study was to examine whether katsuobushi, smoked-dried bonito (KB), which is a traditional Japanese food, prevents ovarian hormone deficiency-induced hypercholesterolemia. In experiment 1, ovariectomized rats (OVX-rats) were fed a purified diet containing casein or KB. Compared with the casein diet, the KB diet reduced the plasma cholesterol concentration and apparent protein digestibility, and increased the fecal dry weight and fecal bile acid excretion. In experiment 2, OVX-rats were fed one of the following four diets: casein diet containing corn oil or fish oil (CA/CO or CA/FO), or a diet containing the digested or undigested fraction of KB after treatment with microbial protease (KBE or KBR). KBR contains mainly two components: oil and protease-undigested protein of KB origin. In comparison with the CA/CO diet, the KBE diet did not affect the plasma and liver lipids concentrations, apparent protein digestibility nor fecal bile acid excretion. However, the KBR and CA/FO diets reduced the plasma cholesterol and triacylglycerol (TAG) concentrations and the liver total lipid and TAG concentrations, but increased the liver total and esterified cholesterol concentrations. The KBR diet increased fecal bile acid excretion and fecal dry weight, whereas the CA/FO diet did not. Thus, the preventive effect of KB on the ovarian hormone deficiency-associated increase in plasma cholesterol concentration appears to be mediated by an increase in bile acid excretion through a promoted secretion of bile acids by the binding of bile acids to resistant proteins.

Immunostimulation effect of jellyfish collagen.

Certain edible large jellyfishes belonging to the order Rhizostomeae are consumed in large quantities in China and Japan. The exumbrella part of the edible jellyfish Stomolophus nomurai was cut and soaked in dilute hydrochloric acid solution (pH 3.0) for 12 h, and heated at 121 degrees C for 20 min. The immunostimulation effects of the jellyfish extract were examined. The jellyfish extract enhanced IgM production of human hybridoma HB4C5 cells 34-fold. IgM and IgG production of human peripheral blood lymphocytes (PBL) were also accelerated, 2.8- and 1.4-fold respectively. Moreover, production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by human PBL was stimulated 100- and 17-fold respectively. Collagenase treatment inactivated the immunostimulation activity of the jellyfish extract. In addition, purified collagen from bovine Achilles' tendon accelerated IgM production of hybridoma cells. These facts mean that collagen has an immunostimulation effect, and that the active substance in jellyfish extract is collagen.