Immunosuppresive action of milk k-casein and its digests

1.牛酪蛋白及其糖巨肽(残基106-169，CGP)至少通过两种不同的机制完全抑制小鼠T淋巴细胞增殖：产生白介素1受体拮抗剂和抑制CD4+T淋巴细胞表面白介素2受体的表达。逆转录聚合酶链式反应分析显示，巨噬细胞转录IL-1受体拮抗剂mRNA，CGP可促进IL-1受体拮抗剂的生物合成和/或分泌，但不影响IL-1α和IL-1β的分泌水平。牛酪蛋白能显著抑制巨噬细胞的活化和吞噬功能。胰酶和胰凝乳酶消化对这两种抑制活性的影响不大，胃酶消化则将抑制活性转化为增强活性。口服牛CGP可抑制小鼠血清中针对饮食蛋白和腹腔注射蛋白的抗体水平。小鼠脾细胞有丝分裂反应表明，添加CGP的小鼠脾细胞抑制性T淋巴细胞数量和/或功能明显增加。人CGP与小鼠淋巴细胞孵育后显示出细胞毒活性。此外，与人CGP孵育的淋巴细胞的染色质发生凝集，从细胞中提取的DNA被分割。这些结果表明，人CGP具有诱导细胞凋亡的能力，用胰酶消化牛CGP也能产生细胞毒活性，提示Kappa-Casein及其消化产物可能参与了新生儿肠道的抗炎反应。此外，由奶酪乳清制成的CGP也可用作制备免疫抑制食品的成分

The results obtained for 2 years (1996 and 1997) are summarized as follows :1. Bovine kappa-casein and it glycomacropeptide (residues 106-169, CGP) completely inhibited mouse T-lymphocyte proliferation via at least 2 different mechanisms : production of interleukin-1 receptor antagonist and suppression of interleukin-2 receptor expression on CD4+ T-lymphocytes.2. Reverse transcription-polymerase chain reaction analysis showed that macrophages transcribed interleukin-1 receptor antagonist mRNA in both the absence and the presence of CGP.CGP increased interleukin-1 receptor antagonist biosynthesis and/or secretion without influencing secretion level of interleukin-1 alpha and interleukin-1 beta.3. Bovine kappa-casein significantly inhibited macrophage activation and phagocytosis of macrophages. Both inhibitory activities was little influenced by trypsin or chymotrypsin digestion while pepsin digestion changed the inhibitory activity into an enhancing activity.4. Orally ingestion of bovine CGP suppressed the level of serum IgG antibodies specific to dietary protein and intraperitoneally injected protein in mice. Mitogenic responses of spleen cells indicated that the suppressor T-lymphocyte number and/or function were significantly increased in mice fed the CGP-added diet.5. Human CGP revealed a cytotoxic activity when the peptide was incubated with mouse lymphocytes. In addition, the chromatin of lymphocytes incubated with human CGP coagulated and DNAs extracted from the cells segmented. These results suggested that human CGP had an apoptosis-inducing ability.Cytotoxic activity was also produced when bovine CGP was digested with trypsin.These results suggest that kappa-casein and its digest may contribute to anti-inflammatory response in neonatal intestine. In addition, CGP prepared from cheese whey is available as an ingredient to prepare immunosuppressive foods