An immunomodulating protein, Ling Zhi-8 (LZ-8) prevents insulitis in non-obese diabetic mice

Abstract

Ling Zhi-8 (LZ-8), a novel and recently discovered immunomodulatory protein having in vivo immuno-suppressive activity, was tested for in vivo effect against Type 1 (insulin-dependent) diabetes mellitus in the nonobese diabetic mouse, the disease having immunologically mediated aetiology in this animal. LZ-8 had mitogenic activity in vitro towards spleen cells of the non-obese diabetic mice as previously shown towards those of DBA/2 mice. Intraperitoneal administration of LZ-8 twice weekly into the mice (10.3-12.6 mg/kg body weight) from 4 weeks of age prevented insulitis and an almost normal number of insulin producing cells were observed. Extreme insulitis and reduction of the number of insulin producing cells were observed in the pancreata of the untreated non-obese diabetic mouse. No cumulative incidence of diabetes mellitus was observed in the LZ-8 treated group, while cumulative incidences of 70% and 60% were observed in an untreated group followed up to 42 weeks of age when the incidence of diabetes was defined as a plasma glucose level of greater than 11 mmol/l and as a urine glucose level of greater than 2+, respectively. T cell subset population analysis was performed to further investigate the action of LZ-8 on the non-obese diabetic mouse which revealed that LZ-8 treatment increased in L3T4'/Lyt-2+ ratio.

Functional expression of LZ-8, a fungal immunomodulatory protein from Ganoderma lucidium in Pichia pastoris

“…As for anti-tumor activity, LZ-8 has been found to be a mitogen in vitro for human peripheral blood lymphocytes, mediated by activating macrophages and T lymphocytes to induce the production of cytokine and tumor necrosis factor-α (Haak-Frendscho et al, 1993;Vander Hem LG et al, 1995). In addition, LZ-8 has also been proved to modify the expression of adhesion molecules on immuno-competent cells (Miyasaka et al, 1992), to suppress autoimmune diabetes in young female non-obese diabetic mice (Kino et al, 1990), and to prevent antibody production and systemic anaphylaxis . Therefore, LZ-8 might be a good candidate for developing a new type of functional food supplements or therapeutic agents to be used for the prevention or treatment of cancer and autoimmune diseases.…”

Clitocypin, a New Type of Cysteine Proteinase Inhibitor from Fruit Bodies of Mushroom Clitocybe nebularis

“…The physiological function of this protein in mushroom is not known. Structurally, it appears to be related to a lectin family of proteins with agglutination activity that have been extensively characterized in several basidiomycete and parasitic deuteromycete fungi such as Ganoderma lucidium (44,45), Agaricus bisporus (46), and Arthrobotrys oligospora (47), where they presumably play a role in fungal growth, morphogenesis, and mycorrhization (48). In contrast to the alignment with cystatin C precursor, the level of identity applies over the entire primary structures.…”

Functional Expression of FIP-gts, a Fungal Immunomodulatory Protein fromGanoderma Tsugaein Sf21 Insect Cells

“…7) As for anti-tumor activity, LZ-8 has been found to be a mitogen in vitro for human peripheral blood lymphocytes, mediated by activating macrophages and T lymphocytes to induce the production of cytokine and tumor necrosis factor-. [8][9][10] In addition, LZ-8 has also been proven to modify the expression of adhesion molecules on immunocompetent cells, 11) to suppress autoimmune diabetes in young female non-obese diabetes mice, 12) and to prevent antibody production and systemic anaphylaxis. 13) Therefore, LZ-8 as well as other FIPs might be good candidates for developing a new type of functional food y To whom correspondence should be addressed.…”