Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR‑155

  • Authors:
    • Caixia Chen
    • Xiulan Su
    • Zhiwei Hu
  • View Affiliations

  • Published online on: July 5, 2019     https://doi.org/10.3892/etm.2019.7734
  • Pages: 1850-1862
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Abstract

The present study was designed to evaluate the effect of bioactive hepatic peptide (BHP) on the immune function of mice and to examine the mechanism mediated by the related factors cytokine suppressor of cytokine signaling 1 (SOCS1) and microRNA (miR)‑155. The mice were divided into eight groups, including a normal mouse group, normal peptide groups (low‑dose, mid‑dose and high‑dose), an immunosuppressed group, and immunosuppressed with peptide groups (low‑dose, mid‑dose and high‑dose). The proliferative ability of splenic lymphocytes was determined in vitro using a Cell Counting kit‑8 assay. Wright's staining was used to assess the phagocytic function of macrophages. Histological changes in the spleen were evaluated by hematoxylin‑eosin staining. The relevant factors SOCS1/miR‑155 were assessed by immunohistochemistry and reverse transcription fluorescence‑quantitative polymerase chain reaction analysis. The levels of the cytokines TGF‑β1, IL‑10 and IL‑17A were determined by enzyme‑linked immunosorbent assay. First, the organ index, percentage of lymphocytes, phagocytosis experiments and splenic lymphocyte proliferation test results revealed that the immunodeficient mouse model had been successfully established. Second, compared with the control mice, the normal peptide group mice exhibited increased spleen and thymus indices, percentages of lymphocyte subsets, macrophage phagocytosis percentages, phagocytic indices, splenic lymphocyte proliferation and expression of miR‑155; however, the expression of SOCS1 was decreased in the normal peptide groups to varying extents. In addition, the expression of SOCS1 was upregulated, whereas that of miR‑155 was downregulated in the immunosuppressed group. Compared with the mice in the immunosuppressed group, the mice in the immunosuppressed with peptide groups had increased spleen and thymus indices, percentages of lymphocyte subsets, macrophage phagocytosis percentages, phagocytic indices, splenic lymphocyte proliferation and expression of miR‑155; however, the expression of SOCS1 was decreased in the immunosuppressed with peptide groups to varying extents. Following treatment with BHP, the secretion of TGF‑β1 in the spleen of the normal mice and immunosuppressed mice was significantly decreased, and the secretion of IL‑10 was significantly increased. No significant difference in the expression of IL‑17A was observed among the groups. In summary, BHP improved the immune function of the normal mice and immunosuppressed mice. This data provides a scientific basis for the development of bioactive peptide health products.

References

1 

McKenzie CG, Guo L, Freedman J and Semple JW: Cellular immune disfunction inimmune thrombocytopenia (ITP). Br J Haematol. 163:10–23. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Xing Z, Yu L, Li X and Su X: Anticancer bioactive peptide-3 inhibits human gastric cancer growth by targeting miR-338-5p. Cell Biosci. 6:532016. View Article : Google Scholar : PubMed/NCBI

3 

Su X, Dong C, Zhang J, Su L, Wang X, Cui H and Chen Z: Combination therapy of anti-cancer bioactive peptide with Cisplatin decreases chemotherapy dosing and toxicity to improve the quality of life in xenograft nude mice bears human gastric cancer. Cell Biosci. 4:7–19. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Słotwiński R, Lech G and Słotwińska SM: Therapeutic microRNAs in human cancer. Cent Eur J Immunol. 43:314–324. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Prabahar A and Natarajan J: ImmunemiR-A database of prioritized immune miRNA disease associations and its interactome. Microrna. 6:71–78. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Zhang Y, Köllmer M, Buhrman JS, Tang MY and Gemeinhart RA: Arginine-rich, cell penetrating peptide-anti-microRNA complexes decrease glioblastoma migration potential. Peptides. 58:83–90. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Xiao C and Rajewsky K: MicroRNA control in the immune system: Basic principles. Cell. 136:26–36. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Escobar T, Yu CR, Muljo SA and Egwuagu CE: STAT3 activates miR-155 in Th17 cells and acts in concert to promote experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 54:4017–4025. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Preston GC, Sinclair LV, Kaskar A, Hukelmann JL, Navarro MN, Ferrero I, MacDonald HR, Cowling VH and Cantrell DA: Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes. EMBO J. 34:2008–2024. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Sobhkhez M, Joensen LL, Tollersrud LG, Strandskog G, Thim HL and Jørgensen JB: A conserved inhibitory role of suppressor of cytokine signaling 1 (SOCS1) in salmon antiviral immunity. Dev Comp Immunol. 67:66–76. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Ma C, Wang Y, Shen A and Cai W: Resveratrol upregulates SOCS1 production by lipopolysaccharide-stimulated RAW264.7 macrophages by inhibiting miR-155. Int J Mol Med. 39:231–237. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Yokoyama WM, Kim S and French AR: The dynamic life of natural killer cells. Annu Rev Immunol. 22:405–429. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Vivier E, Tomasello E, Baratin M, Walzer T and Ugolini S: Functions of natural killer cells. Nat Immunol. 9:503–510. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Sullivan RP, Fogel LA, Leong JW, Schneider SE, Wong R, Romee R, Thai TH, Sexl V, Matkovich SJ, Dorn GW II, et al: miR-155 tunes both the threshold and extent of NK cell activation via targeting of multiple signaling pathways. J Immunol. 191:5904–5913. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, Loeb GB, Lee H, Yoshimura A, Rajewsky K and Rudensky AY: Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 30:80–91. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Banerjee A, Schambach F, DeJong CS, Hammond SM and Reiner SL: Micro-RNA-155 inhibits IFN-gamma signaling in CD4+ T cells. Eur J Immunol. 40:225–231. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Okoye IS, Czieso S, Ktistaki E, Roderick K, Coomes SM, Pelly VS, Kannan Y, Perez-Lloret J, Zhao JL, Baltimore D, et al: Transcriptomics identifieda critical role for Th2 cell-intrinsic miR-155 in mediating allergy andantihelminth immunity. Proc Natl Acad Sci USA. 111:E3081–E3090. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X and Liao YH: MicroRNA-155 modulates treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS One. 7:e460822012. View Article : Google Scholar : PubMed/NCBI

19 

Yan L, Hu F, Yan X, Wei Y, Ma W, Wang Y, Lu S and Wang Z: Inhibition of microRNA-155 ameliorates experimental autoimmune myocarditis by modulating Th17/Treg immune response. J Mol Med (Berl). 94:1063–1079. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Babicz-Zielinska E and Jezewska-Zychowicz M: Conceptual model of consumer's willingness to eat functional foods. Rocz Panstw Zakl Hig. 68:33–41. 2017.PubMed/NCBI

21 

Bose U, Hodson MP, Shaw PN, Fuerst JA and Hewavitharana AK: Two peptide, cycloaspeptide A and nazumamide A from a sponge associated marine actinobacterium Salinispora sp. Nat Prod Commun. 9:545–546. 2014.PubMed/NCBI

22 

Pessione E and Cirrincione S: Bioactive molecules released in food by lactic acid bacteria: Encrypted peptides and biogenic amines. Front Microbiol. 7:8762016. View Article : Google Scholar : PubMed/NCBI

23 

Silk DB, Grimble GK and Rees RG: Protein digestion and amino acid and peptide absorption. Proc Nutr Soc. 44:63–72. 1985. View Article : Google Scholar : PubMed/NCBI

24 

Su X, Chen C, Liu Q, She Y, Yan M and Hou J: Preparation method of anti-gastric cancer bioactive peptide. China Patent ZL96122236.0. Filed November 4, 1996; issued September 4, 2000.

25 

Li L, Yu L, Hu J, et al: Establishment of separation and identification methods for bioactive peptide protein components. Sheng Wu Ji Shu Tong Xun. 25:682–686. 2014.

26 

Crago SS, Prince SJ, Pretlow TG, McGhee JR and Mestecky J: Human colostral cells. I. Separation and characterization. Am J Clin Exp Immunol. 38:585–597. 1979.

27 

Shen QC, Lin Y, Wang SY, et al: Identification and culture of Buffalo peripheral blood mononuclear macrophage. China Animal Husbandry & Veterinary Medicine. 38:31–35. 2011.

28 

Stevenson HC, Katz P, Wright DG, Contreras TJ, Jemionek JF, Hartwig VM, Flor WJ and Fauci AS: Human blood monocytes: Characterization of negatively selected human monocytes and their suspension cell culture derivatives. Scand J Immunol. 14:243–256. 1981. View Article : Google Scholar : PubMed/NCBI

29 

Ji H, Tian D, Zhang B, Zhang Y, Yan D and Wu S: Overexpression of miR-155 in clear-cell renal cell carcinoma and its oncogenic effect through targeting FOXO3a. Exp Ther Med. 13:2286–2292. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Zhang SP, Wang W, Gu Y, Jin L and Zhou F: Study on the correlation between ultrasonic imaging features in breast cancer and the expression of ER, PR, HER-2 and nm23. Biomedical Res. 28:5925–5929. 2017.

31 

Ke M, Wang H, Zhou Y, Li J, Liu Y, Zhang M, Dou J, Xi T, Shen B and Zhou C: SEP enhanced the antitumor activity of 5-fluorouracil by up-regulating NKG2D/MICA and reversedimmune suppressionvia inhibiting ROS and caspase-3 in mice. Oncotarget. 7:49509–49526. 2016. View Article : Google Scholar : PubMed/NCBI

32 

Zhou G, Wang D, Liu D, Qi D and Liu Z: Expression of B and T lymphocyte attenuator in patients with severe community-acquired pneumonia and the effect of steroid therapy in a mouse model. Clin Lab. 62:2367–2377. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Pavić I, Katalinić-Janković V, Čepin-Bogović J, Rešić A and Dodig S: Discordance between tuberculin skin test and interferon-γ release assay in children younger than 5 years who have been vaccinated with bacillus calmette-guérin. Lab Medicine. 46:200–206. 2015. View Article : Google Scholar

34 

Janossy G, Snajdr J and Simakellis M: Patterns of B-lymphocyte gene expression elicited by lipopolysaccharide mitogen. Immunology. 30:799–810. 1976.PubMed/NCBI

35 

Smialek M, Tykalowski B, Dziewulska D, Stenzel T and Koncicki A: Immunological aspects of the efficiency of protectotype vaccination strategy against chicken infectious bronchitis. BMC Vet Res. 13:1–44. 2017.PubMed/NCBI

36 

Yu Y, Wang H, Meng X, Hao L, Fu Y, Fang L, Shen D, Yu X and Li J: Immunomodulatory effects of cinobufagin on murine lymphocytes and macrophages. Evid Based Complement Alternat Med. 2015:8352632015. View Article : Google Scholar : PubMed/NCBI

37 

Bernard M, Furlong SJ, Power Coombs MR and Hoskin DW: Differential inhibition of T lymphocyte proliferation and cytokine synthesis by [6]-Gingerol, [8]-Gingerol, and [10]-Gingerol. Phytother Res. 29:1707–1713. 2015. View Article : Google Scholar : PubMed/NCBI

38 

Nicholson LB: The immune system. Essays Biochem. 60:275–301. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Tsai CY, Allie SR, Zhang W and Usherwood EJ: MicroRNA miR-155 affects antiviral effector and effector memoryCD8 T cell differentiation. J Virol. 87:2348–2351. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Shi J, Bo S and Miao M: Effect of Astragalus polysaccharide on immunological function of immunosuppressive mice induced by cyclophosphamide. Zhong Yi Xue Bao. 31:243–246. 2016.

41 

Cai K, Wang X, Zhang B, et al: Effects of Curculigo chinensis polysaccharides on immune function in immunosuppressed mice induced by cyclophosphamide. Zhong Hua Zhong Yi Yao Za Zhi. 148–152. 2016.

42 

Zhu X, Xu D, Chen X, et al: Immunomodulatory effects of black chicken peptide on cyclophosphamide-induced immunocompromised mice. Shi Pin Yu Fa Jiao Gong Ye. 42:44–49. 2016.

43 

Zak DE, Tam VC and Aderem A: Systems-level analysis of inna-teImmunity. Annu Rev Immunol. 32:547–577. 2014. View Article : Google Scholar : PubMed/NCBI

44 

Leong JW, Sullivan RP and Fehniger TA: microRNA managem-of NK-cell developmental and functional programs. Eur J Immunol. 44:2862–2868. 2014. View Article : Google Scholar : PubMed/NCBI

45 

Seregin SS and Amalfitano A: Improving adenovirus based gene transfer: Strategies to accomplish immune evasion. Viruses. 2:2013–2036. 2010. View Article : Google Scholar : PubMed/NCBI

46 

Gemperle C, Schmid M, Herova M, Marti-Jaun J, Wuest SJ, Loretz C and Hersberger M: Regulation of the formyl peptide receptor 1 (FPR1) gene in primary human macrophages. PLoS One. 7:1–6. 2012. View Article : Google Scholar

47 

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, et al: Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313:1960–1964. 2006. View Article : Google Scholar : PubMed/NCBI

48 

Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, Gritti G, Corradini P, Di Nicola M, Patti C, et al: Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. J Clin Oncol. 34:4015–4022. 2016. View Article : Google Scholar : PubMed/NCBI

49 

Wang S, Zheng Q, Tian F, et al: Changes of microRNA expression profiles during NKT cell development. Zhong Guo Mian Yi Xue Za Zhi. 33:979–984. 2017.

50 

Shaohua S: Research progress in the regulation of SOCS1 on immune response in the body. Chin J Med Officer. 35:1035–1037. 2010.

51 

Liu Y: Mechanism of MiR-155 regulating T cell activation. PhD dissertation, Di Er Jun Yi Da Xue. CNKI; Beijing: 2011

52 

Liu Y and Cheng X: Research Progress of MicroRNA on host immunity regulation. Xian Dai Mian Yi Xue. 432–435. 2011.

53 

Zhang Y, Alexander PB and Wang XF: TGF-β family signaling in the control of cell proliferation and survival. Cold Spring Harb Perspect Biol. 9(pii): a0221452017. View Article : Google Scholar : PubMed/NCBI

54 

Komai T, Okamura T, Yamamoto K and Fujio K: The effects of TGF-βs on immune responses. Nihon Rinsho Meneki Gakkai Kaishi. 39:51–58. 2016. View Article : Google Scholar : PubMed/NCBI

55 

Saraiva M and Garra A: The regulation of IL-10 production by immune Cells. Nat Rev Immunol. 10:170–181. 2010. View Article : Google Scholar : PubMed/NCBI

56 

MacNeil IA, Suda T, Moore KW, Mosmann TR and Zlotnik A: IL-10, a novel growth cofactor for mature and immature T cells. J Immunol. 145:4167–4173. 1990.PubMed/NCBI

57 

Rutz S and Ouyang W: Regulation of interleukin-10 expression. Adv Exp Med Biol. 941:89–116. 2016. View Article : Google Scholar : PubMed/NCBI

58 

Cao W, Chen W, Liang X, Zhou J, Wei C, Cui S and Liu J: All-trans-retinoic acid ameliorates the inflammation by inducing transforming growth factor beta 1 and interleukin 10 in mouse epididymitis. Am J Reprod Immunol. 71:312–321. 2014. View Article : Google Scholar : PubMed/NCBI

59 

Zhang X, Jiang Z, Gu Y, Liu Y, Cao X and Han Y: Inflammation-induced CD69+Kupffer cell feedback inhibits T cell proliferation via membrane-bound TGF-β1. Sci China Life Sci. 59:1259–1269. 2016. View Article : Google Scholar : PubMed/NCBI

60 

Ji H, Li Y, Jiang F, Wang X, Zhang J, Shen J and Yang X: Inhibition of transforming growth factor beta⁄SMAD signal by MiR-155 is involved in arsenic trioxideinduced anti-angiogenesis in prostate cancer. Cancer Sci. 105:1541–1549. 2014. View Article : Google Scholar : PubMed/NCBI

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APA
Chen, C., Su, X., & Hu, Z. (2019). Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR‑155. Experimental and Therapeutic Medicine, 18, 1850-1862. https://doi.org/10.3892/etm.2019.7734
MLA
Chen, C., Su, X., Hu, Z."Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR‑155". Experimental and Therapeutic Medicine 18.3 (2019): 1850-1862.
Chicago
Chen, C., Su, X., Hu, Z."Immune promotive effect of bioactive peptides may be mediated by regulating the expression of SOCS1/miR‑155". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1850-1862. https://doi.org/10.3892/etm.2019.7734