Fungal immunomodulatory proteins 7 regulating the innate immune and adaptive immune responses. and oLB2 on the surface of macrophages.LZ-8 can enhance Cytokines possess lymphocyte proliferation,immune cells the expression of ICAM-1.Haak-Frendscho regarded LZ-8 activation and tumor inhibition effects.Based on recent as aT cell activator,which has its effect via cytokine regulation reports,LZ-8 could induce the production of IL-2 and the (Haak-Frendscho et al.,1993).FIP-fve induces the expression corresponding up-regulated expression of IL-2 receptor.It of ICAM-1 in hPMCs in a dose dependent manner.FIP-fve also regulates the expression of IL-1B(IFN-Y,and TNF-c (Li is also considered as a T cell activator,it is involved in immune et al.,2011).ReLZ-8 can enhance the expression level of IL- regulation through p38MAPK(mitogen-activated protein 2,TNF-o as well as-the ratio of IL-2/IL-4 (Bai et al.,2006; kinase)pathway and it activates Th,cells to secrete IFN-Y Yeh et al.,2008;Lin et al.,2008).FIP-vvo can significantly (Wang et al.,2004;Li et al.,2011). increase the expression level of IL-2,IL-4,IFN-Y,TNF-a,LT, and IL-2 receptor with dose dependent effect.However,it Anti-Allergic Effects cannot increase the expression of IL-1,IL-3,IL-5 and IL-6 (Hsu et al.,1997;Li et al.,2011).FIP-vvo mainly acts on Th, IgE is the main cause of allergic reaction,and the production cells and to a lesser extent on Th,cells in the early event of of IgE depends on IL-4.LZ-8 and the FIP-fve have significant activation (Moradali et al.,2007).FIP-fve activates Th, inhibition on systemic allergic reactions caused by bovine triggers cytokines release,inhibits Th,cells and indirectly serum albumin(BSA).However,this effect of FIP-vvo is not suppresses IgE secretion.FIP-fve increases the mRNA obvious (Kino et al.,1989;Ko et al.,1995;Hsu et al.,1997) expression levels of IL-2 and IFN-y in spleen cells in a dose LZ-8 can inhibit the systemic allergic reactions.Haak- dependent manner (Ko et al.,1995).Noticeably,IL-2's Frendscho et al found that LZ-8 could induce the production expression level,under the induction of FIP which is expressed of IL-2 (Haak-Frendscho et al.,1993).Yeh et al.later in baculovirus infected insect cells,is much higher than those confirmed that LZ-8 could increase the ratio of IL-2/IL-4 expressed in prokaryotic host cells (Wu et al.,2008).In vitro, (Yeh et al.,2008).FIP-fve is also capable to inhibit the systemic peritoneal cells of mice are treated with the LPS,FIP-fve could allergic reactions.FIP-fve is able to induce hPBMCs to increase the production of abdominal TNF-o.and nitric oxide produce high level of IFN-Y (Wang et al.,2004).However, (NO)as well as enhancing the cancer killing ability of FIP-vvo does not inhibit the systemic allergic reactions.FIP- peritoneal cells(Hsieh et al,2003).By subcutaneous injection vvo can also induce IL-4.Thus,Hsu et al.hypothesized that of FIP-fve in mice,Kong and his group analyze the changing it is the enhanced expression of IL-4 that reduces the ability level of IFN-y and IL-4 in serum by enzyme linked immuno- of FIP-vvo to inhibit systemic allergic reactions (Hsu et al., sorbent assay (ELISA).Results showed that there were 1997). significant increased of IFN-y levels in serum,however,IL-4 Arthus reaction would cause dropsy of the footpad,and levels were slightly increased (Kong et al.,2007). FIPs are able to reduce the thickness of BSA-induced footpad Immunomodulation by fungal compounds,especially FIPs, in mice.After treatment of LZ-8,only 40%of the CFW mice can be determined by the capacity of the compounds to that have Arthus reaction caused by BSA appear footpad influence the cytokine production by hPBMCs.The protein edema (Kino et al.,1989).With the treatment of 5 mg/kg or and polysaccharides isolated and purified from eight 20 mg/kg FIP-fve on Bal b/C mice,Arthus reaction is reduced mushroom strains (Agaricus blazei,Coprinus comatus,F. to 13.7%and 49.3%accordingly (Ko et al.,1995).FIP-vvo velutipes,G.lucidum,Grifola frondosa,V volvacea,Lentinus is capable of reducing the Arthus reaction on mice induced edodes,and Pleurotus ostreatus)in mycelia and culture by the BSA,Hsu et al showed that only 40%of mice treated medium,are tested for the immunomodulatory activity.In with BSA and FIP-yvo resulted in pad edema (Hsu et al., vitro,hPBMCs is stimulated with Propylene Glycol 1997). Monomethyl Acetate (PMA)/Ca-I,concanavaline A(ConA) In vivo,it has been proven many times that LZ-8 has anti- or lipopolysaccharide(LPS)to increase expression level of allergic effects,but the mechanism is yet unclear.Initial cytokines IFN-Y,IL-4,IL-10,IL-12 and TNF-a.Due to these hypothesis is that it is due to the inhibition of antibody stimuli,the proteins of G.lucidum and V.volvacea show formation.Two types of Fc receptors have been reported.One immunomodulatory effects,they reduce the expression level is on the surface of basophiles and mast cells with high affinity of IL-4 and IFN-Y.This effect might lead to the indirect for IgE,and another on the cell surface ofT or B lymphocytes immunomodulation of T cell activation and cytokine with low affinity.The latter one may be important for the production (Jeurink et al.,2008). regulation of selective IgE production by secreting two IgE binding factors,one with potentiating and the other with Activation of Cell Adhesion Molecules suppressing activity toward IgE production(Kino et al.,1989). FIP-fve has effects on immunomodulation and lymphocytes Intercellular adhesion molecule-1 (ICAM-1)is a member proliferation,as well as inhibition of allergy in Bal b/c mice of the immunoglobulin superfamily,which is involved in cell- system.Mice are caused allergic by subcutaneous or cell adhesion ICAM on the stimulated endothelial cell surface intraperitoneal injection of BSA,and strengthen immunization can combine with aLB2 on the surface of white blood cells after 17d via the injection of BSA.All mice suffered fromFungal immunomodulatory proteins 7 regulating the innate immune and adaptive immune responses. Cytokines possess lymphocyte proliferation, immune cells activation and tumor inhibition effects. Based on recent reports, LZ-8 could induce the production of IL-2 and the corresponding up-regulated expression of IL-2 receptor. It also regulates the expression of IL-1β(IFN-γ, and TNF-α (Li et al., 2011). ReLZ-8 can enhance the expression level of IL- 2, TNF-α as well as the ratio of IL-2/IL-4 (Bai et al., 2006; Yeh et al., 2008; Lin et al., 2008). FIP-vvo can significantly increase the expression level of IL-2, IL-4, IFN-γ, TNF-α, LT, and IL-2 receptor with dose dependent effect. However, it cannot increase the expression of IL-1, IL-3, IL-5 and IL-6 (Hsu et al., 1997; Li et al., 2011). FIP-vvo mainly acts on Th1 cells and to a lesser extent on Th2 cells in the early event of activation (Moradali et al., 2007). FIP-fve activates Th1 , triggers cytokines release, inhibits Th2 cells and indirectly suppresses IgE secretion. FIP-fve increases the mRNA expression levels of IL-2 and IFN-γ in spleen cells in a dose dependent manner (Ko et al., 1995). Noticeably, IL-2’s expression level, under the induction of FIP which is expressed in baculovirus infected insect cells, is much higher than those expressed in prokaryotic host cells (Wu et al., 2008). In vitro, peritoneal cells of mice are treated with the LPS, FIP-fve could increase the production of abdominal TNF-α and nitric oxide (NO) as well as enhancing the cancer killing ability of peritoneal cells (Hsieh et al., 2003). By subcutaneous injection of FIP-fve in mice, Kong and his group analyze the changing level of IFN-γ and IL-4 in serum by enzyme linked immuno￾sorbent assay (ELISA). Results showed that there were significant increased of IFN-γ levels in serum, however, IL-4 levels were slightly increased (Kong et al., 2007). Immunomodulation by fungal compounds, especially FIPs, can be determined by the capacity of the compounds to influence the cytokine production by hPBMCs. The protein and polysaccharides isolated and purified from eight mushroom strains (Agaricus blazei, Coprinus comatus, F. velutipes, G. lucidum, Grifola frondosa, V. volvacea, Lentinus edodes, and Pleurotus ostreatus) in mycelia and culture medium, are tested for the immunomodulatory activity. In vitro, hPBMCs is stimulated with Propylene Glycol Monomethyl Acetate (PMA)/Ca-I, concanavaline A (ConA) or lipopolysaccharide (LPS) to increase expression level of cytokines IFN-γ, IL-4, IL-10, IL-12 and TNF-α. Due to these stimuli, the proteins of G. lucidum and V. volvacea show immunomodulatory effects, they reduce the expression level of IL-4 and IFN-γ. This effect might lead to the indirect immunomodulation of T cell activation and cytokine production (Jeurink et al., 2008). Activation of Cell Adhesion Molecules Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, which is involved in cell￾cell adhesion ICAM on the stimulated endothelial cell surface can combine with αLβ2 on the surface of white blood cells and αLβ2 on the surface of macrophages. LZ-8 can enhance the expression of ICAM-1. Haak-Frendscho regarded LZ-8 as a T cell activator, which has its effect via cytokine regulation (Haak-Frendscho et al., 1993). FIP-fve induces the expression of ICAM-1 in hPMCs in a dose dependent manner. FIP-fve is also considered as a T cell activator, it is involved in immune regulation through p38MAPK (mitogen-activated protein kinase) pathway and it activates Th1 cells to secrete IFN-γ (Wang et al., 2004; Li et al., 2011). Anti-Allergic Effects IgE is the main cause of allergic reaction, and the production of IgE depends on IL-4. LZ-8 and the FIP-fve have significant inhibition on systemic allergic reactions caused by bovine serum albumin (BSA). However, this effect of FIP-vvo is not obvious (Kino et al., 1989; Ko et al., 1995; Hsu et al., 1997). LZ-8 can inhibit the systemic allergic reactions. Haak￾Frendscho et al. found that LZ-8 could induce the production of IL-2 (Haak-Frendscho et al., 1993). Yeh et al. later confirmed that LZ-8 could increase the ratio of IL-2/IL-4 (Yeh et al., 2008). FIP-fve is also capable to inhibit the systemic allergic reactions. FIP-fve is able to induce hPBMCs to produce high level of IFN-γ (Wang et al., 2004). However, FIP-vvo does not inhibit the systemic allergic reactions. FIP￾vvo can also induce IL-4. Thus, Hsu et al. hypothesized that it is the enhanced expression of IL-4 that reduces the ability of FIP-vvo to inhibit systemic allergic reactions (Hsu et al., 1997). Arthus reaction would cause dropsy of the footpad, and FIPs are able to reduce the thickness of BSA-induced footpad in mice. After treatment of LZ-8, only 40% of the CFW mice that have Arthus reaction caused by BSA appear footpad edema (Kino et al., 1989). With the treatment of 5 mg/kg or 20 mg/kg FIP-fve on Bal b/C mice, Arthus reaction is reduced to 13.7% and 49.3% accordingly (Ko et al., 1995). FIP-vvo is capable of reducing the Arthus reaction on mice induced with BSA and FIP-vvo resulted in pad edema (Hsu et al., 1997). In vivo, it has been proven many times that LZ-8 has anti￾allergic effects, but the mechanism is yet unclear. Initial hypothesis is that it is due to the inhibition of antibody formation. Two types of Fc receptors have been reported. One is on the surface of basophiles and mast cells with high affinity with low affinity. The latter one may be important for the regulation of selective IgE production by secreting two IgE binding factors, one with potentiating and the other with suppressing activity toward IgE production (Kino et al., 1989). FIP-fve has effects on immunomodulation and lymphocytes proliferation, as well as inhibition of allergy in Bal b/c mice system. Mice are caused allergic by subcutaneous or intraperitoneal injection of BSA, and strengthen immunization after 17d via the injection of BSA. All mice suffered from by the BSA, Hsu et al showed that only 40% of mice treated for IgE, and another on the cell surface of T or B lymphocytes