The immune deficiency caused by aging deserves attention, especially the weakening of intestinal mucosal immunity. The effect of β-casomorphin-7 on intestinal mucosal immunity was investigated in aged mice. Mice were treated without or with different doses of β-casomorphin-7 for 30 days. Histopathological studies showed the tissue protective role of β-casomorphin-7 in aged mice. Lowdose group could significantly increase the level of IL-2 and TNF-α in intestinal mucosa. A significant increase in the level of SIgA was observed in medium- and high-dose groups. The low and medium dose groups could significantly increase the activity of SOD in small intestine mucosa. All dose groups significantly reduced the levels of MDA. The results suggest that β-casomorphin-7 could improve intestinal mucosal immune decline which is induced by aging The mechanisms for the regulating effects were likely through balancing the cytokine level and controlling the oxidative stress.
Yaşlanmaya bağlı bağışıklık yetersizliği özellikle bağırsak mukozası bağışıklığı olmak üzere dikkat edilmesi gereken bir husustur. Bu çalışmada, yaşlı farelerin bağırsak mukozası bağışıklığına β-kazomorfin-7’nin etkisi araştırılmıştır. Farelere 30 gün süresince farklı dozlarda β-kazomorfin-7 içeren veya içermeyen uygulamalar yapıldı. Histopatolojik incelemelerde β-kazomorfin-7’nin yaşlı farelerde doku koruyucu etkisinin olduğu gözlemlendi. Düşük doz grubunda bağırsak mukozasında IL-2 ve TNF-α seviyeleri anlamlı derecede arttı. Orta ve yüksek doz gruplarında SIgA seviyesinde anlamlı bir artma gözlemlendi. Düşük ve orta doz gruplarında ince bağırsak mukozasında SOD aktivitesi anlamlı derecede arttı. Tüm doz gruplarında, MDA aktivitesi anlamlı derecede azaldı. Elde edilen sonuçlar, β-kazomorfin-7’nin yaşlılığa bağlı olarak gelişen bağırsak mukozası bağışıklığında meydana gelen düşüşü iyileştirebileceğini gösterdi. Bu düzenleyici etkiyi muhtemelen sitokin seviyesi ve oksidatif stresi kontrol altında tutmak suretiyle oluşturmaktadır.
___
1. García-Peña C, Álvarez-Cisneros T, Quiroz-Baez R, Friedland RP: Microbiota and aging. A review and commentary. Arch Med Res, 48 (8): 681-689, 2017. DO: 10.1016/j.arcmed.2017.11.005
2. Nagura H: Mucosal immune system in health and disease. Pathol Int, 42 (6): 387-400, 1992. DOI: 10.1111/j.1440-1827.1992.tb03243.x
3. Darewicz M, Iwaniak A, Minkiewicz P: Biologically active peptides derived from milk proteins. Pol J Food Nutr Sci, 58 (6): 289-294, 2014.
4. Brantl V, Teschemacher H, Henschen A, Lottspeich F: Novel opioid peptides derived from casein (β-casomorphins). I. Isolation from bovine casein peptone. Hoppe Seylers Z Physiol Chem, 360 (2): 1211-1216, 1979.
5. Yin H, Miao JF, Zhang YS: Protective effect of β-casomorphin-7 on type 1 diabetes rats induced with streptozotocin. Peptides, 31, 1725– 1729, 2010. DOI: 10.1016/j.peptides.2010.05.016
6. Yin H, Miao J, Ma C, Sun GJ, Zhang YS: β -Casomorphin-7 cause decreasing in oxidative stress and inhibiting NF-κB-iNOS-NO signal pathway in pancreas of diabetes rats. J Food Sci, 77 (2): C278–C282, 2012. DOI: 10.1111/j.1750-3841.2011.02577.x
7. Zhang W, Miao J, Wang S, Zhang Y: The protective effects of β -casomorphin-7 against glucose-induced renal oxidative stress in vivo and vitro. Plos One, 8 (5): e63472, 2013. DOI: 10.1371/journal. pone.0063472
8. Kaminski S, Cieslinska A, Kostyra E: Polymorphism of bovine betacasein and its potential effect on human health. J Appl Genet, 48 (3): 189- 198, 2007. DOI: 10.1007/BF03195213
9. Zong YF, Chen WH, Zhang YS, Zou SX: Effects of intra-gastric betacasomorphin- 7 on somatostatin and gastrin gene expression in rat gastric mucosa. World J Gastroenterol, 13 (14): 2094-2099, 2007. DOI: 10.3748/wjg.v13.i14.2094
10. Sozmen B, Delen Y, Girgin FK, Sozmen EY: Catalase and paraoxonase in hypertensive type 2 diabetes mellitus: Correlation with glycemic control. Clin Biochem, 32 (6): 423-427, 1999. DOI: 10.1016/S0009-9120(99)00034-X
11. Knodler LA, Crowley SM, Sham HP, Yang H, Wrande M, Ma C, Ernst RK, Steele-Mortimer O, Celli J, Vallance BA: Non-canonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe, 16 (2): 249-256, 2014. DOI: 10.1016/j.chom.2014.07.002
12. De Barros Alencar AC, Neves RH, de Oliveira AV, Machado-Silva JR: Changes in the small intestine of Schistosoma mansoni-infected mice fed a high-fat diet. Parasitol, 139 (6): 716-725, 2012. DOI: 10.1017/ S0031182011002307
13. Liang Z, Xie Y, Dominguez JA, Breed ER, Yoseph BP, Burd EM, Farris AB, Davidson NO, Coopersmith CM: Intestine-specific deletion of microsomal triglyceride transfer protein increases mortality in aged mice. Plos One, 9 (7): e101828, 2014. DOI: 10.1371/journal.pone.0101828
14. Thomas S, Kenneth D, Livak J: Analyzing real-time PCR data by comparative CT method. Nat Protoc, 3 (6): 1101-1108, 2008.
15. Ershler WB, Keller ET: Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med, 51 (1): 245-270, 2000. DOI: 10.1146/annurev.med.51.1.245
16. Ponnappan S, Ponnappan U: Aging and immune function: Molecular mechanisms to interventions. Antioxid Redox Signal, 14 (8): 1551-1585, 2011. DOI: 10.1089/ars.2010.3228
17. Miró L, Garciajust A, Amat C, Polo J, Moreto M, Perez-Bosque A: Dietary animal plasma proteins improve the intestinal immune response in senescent mice. Nutrients, 9 (12): 1346, 2017. DOI: 10.3390/ nu9121346
18. Man AL, Gicheva N, Nicoletti C: The impact of ageing on the intestinal epithelial barrier and immune system. Cell Immunol, 289 (1-2): 112-118, 2014. DOI: 10.1016/j.cellimm.2014.04.001
19. Watabe T, Nagaishi T, Hosoya A, Jose N , Tokai A, Kojima Y, Adachi T, Watanabe T: The lack of secreted IgA spontaneously induces the mucosal inflammation specifically in the ileum. Gastroenterology, 152 (5): S1004, 2017.
20. Zhao L, Ma LY: Animal experiment of casein peptide in delaying senility. Food Ind, 5, 11-12, 2010.
21. Na S, Kim OS, Ryoo S, Kweon TD, Choi YS, Shim HS, Oh YJ: Cervical ganglion block attenuates the progression of pulmonary hypertension via nitric oxide and arginase pathways. Hypertension, 63 (2): 309-315, 2014. DOI: 10.1161/HYPERTENSIONAHA.113.01979
22. Bozukluhan K, Atakisi E, Atakisi O: Nitric oxide levels, total antioxidant and oxidant capacity in cattle with foot-and-mouth-disease. Kafkas Univ Vet Fak Derg, 19 (1): 179-181, 2013. DOI: 10.9775/kvfd.2012.7244
23. Kajita M, Hikosaka K, Iitsuka M, Kanayama A, Toshima N, Miyamoto Y: Platinum nanoparticle is a useful scavenger of superoxide anion and hydrogen peroxide. Free Radic Res, 41 (6): 615-626, 2007. DOI: 10.1080/10715760601169679
24. Cho SC, Chao YY, Hong CY, Kao CH: The role of hydrogen peroxide in cadmium-inhibited root growth of rice seedlings. Plant Growth Regul, 66 (1): 27-35, 2012. DOI: 10.1007/s10725-011-9625-7