Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Kinetics and Biological Function of Transforming Growth Factor-$\beta$ Isoforms in Bovine and Human Colostrum

  • CHUN, SUNG-KI (Department of Microbiology, Kangwon National University) ;
  • NAM, MYOUNG-SOO (Department of Dairy Science, College of Agriculture, Chungnam National University) ;
  • GOH, JUHN-SU (Department of Animal Products Science and Vascular System Research Center, Kangwon National University) ;
  • KIM, WAN-SUP (Dairy Science Laboratory, Graduate School of Agriculture, Hokkaido University) ;
  • HAN, YOUNG-HWAN (Department of Biology, College of Natural Sciences, Dongguk University) ;
  • KIM, PYEUNG-HYEUN (Department of Microbiology, Kangwon National University, Vascular System Research Center, Kangwon National University) ;
  • Published : 2004.12.01
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Abstract

Colostrum contains various kinds of cytokines including TGF-$\beta$ that has potent regulatory effects on cells of the immune system. We compared the levels of TGF-$\beta$1 and TGF-$\beta$2 in bovine and human colostrum. Based on the isoform-specific ELISA, bovine colostrum collected on day 1 post-delivery retained $53.71{\pm}29.55\;ng/ml$ of TGF-$\beta$1 and $40.41{\pm}21.78\;{\mu}g/ml$ of TGF-$\beta$2 (n=4), while in human, $381.45{\pm}158.24\;ng/ml$ of TGF-$\beta$1 and $41.47{\pm}9.63\;ng/ml$ of TGF-$\beta$2 (n=5). Thus, dominant TGF-$\beta$ isoforms were completely opposite between human and bovine colostrum samples. The concentrations of both isoforms declined as lactation proceeded. Biological activities of the colostrum samples were determined using an MV1LU cell line. Consistent with the result from the immunoassay, TGF-$\beta$1 in human and TGF-$\beta$2 in bovine colostrum were responsible for the anti proliferative activity against MV1LU cells. Furthermore, bovine colostrum increased IgA secretion by LPS-stimulated mesenteric lymph node (MLN) cells, and this effect was abrogated by either anti­TGF-$\beta$2 antibody or combined anti-TGF-$\beta$1/$\beta$2 antibody, but not by anti- TGF-$\beta$1 antibody alone. Similarly, TGF-$\beta$2 in bovine colostrum enhanced the Ig germ line (GL) promoter activity, which is the earliest event toward IgA isotype switching. Taken together, these results suggest that TGF-$\beta$ isoforms, differentially expressed in human and bovine colostrum, may promote IgA isotype production in the neonatal intestine.

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References

  1. Bartram, U., D. G. Molin, L. J. Wisse, A. Mohamad, L. P. Sanford, T. Doetschman, C. P. Speer, R. E. Poelmann, and A. C. Gittenberger-de Groot. 2001. Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGF-beta(2)- knockout mice. Circulation 103: 2745-2752
  2. Danielpour, D., L. L. Dart, K. C. Flanders, A. B. Roberts, and M. B. Sporn. 1989. Immunodetection and quantitation of the two forms of transforming growth factor-beta (TGFbeta 1 and TGF-beta 2) secreted by cells in culture. J. Cell Physiol. 138: 79-86 https://doi.org/10.1002/jcp.1041380112
  3. Ginjala, V. and R. Pakkanen. 1998. Determination of transforming growth factor-beta 1 (TGF-beta 1) and insulinlike growth factor (IGF-1) in bovine colostrum samples. J. Immunoassay 19: 195-207
  4. Harpel, J. G., C. N. Metz, S. Kojima, and D. B. Rifkin. 1992. Control of transforming growth factor-beta activity: Latency vs. activation. Prog. Growth Factor Res. 4: 321-335
  5. Heldin, C. H., K. Miyazono, and P. ten Dijke. 1997. TGFbeta signalling from cell membrane to nucleus through SMAD proteins. Nature 390: 465-471
  6. Islam, K. B., L. Nilsson, P. Sideras, L. Hammarstrom, and C. I. Smith. 1991. TGF-beta 1 induces germ-line transcripts of both IgA subclasses in human B lymphocytes. Int. Immunol. 3: 1099-1106
  7. Kalliomaki, M., A. Ouwehand, H. Arvilommi, P. Kero, and E. Isolauri. 1999. Transforming growth factor-beta in breast milk: A potential regulator of atopic disease at an early age. J. Allergy Clin. Immunol. 104: 1251-1257 https://doi.org/10.1016/S0091-6749(99)70021-7
  8. Kanzaki, T., A. Olofsson, A. Moren, C. Wernstedt, U. Hellman, K. Miyazono, L. Claesson-Welsh, and C. H. Heldin. 1990. TGF-beta 1 binding protein: A component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell 61: 1051-1061
  9. Kim, P. H. and M. F. Kagnoff. 1990. Transforming growth factor-beta 1 is a costimulator for IgA production. J. Immunol. 144: 3411-3416
  10. Kim, Y. J., M. C. Lee, Y. E. Park, H. T. Kim, E. Y. Choi, W. H. Byeon, and P. H. Kim. 1994. Immunodetection of transforming growth factor-beta1 by an improved enzymelinked immunosorbent assay. Kor. J. Immunol. 16: 171-176
  11. Kulkarni, A. B., C. G. Huh, D. Becker, A. Geiser, M. Lyght, K. C. Flanders, A. B. Roberts, M. B. Sporn, J. M. Ward, and S. Karlsson. 1993. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc. Natl. Acad. Sci. USA 90: 770-774
  12. Kulkarni, A. B., T. Thyagarajan, and J. J. Letterio. 2002. Function of cytokines within the TGF-beta superfamily as determined from transgenic and gene knockout studies in mice. Curr. Mol. Med. 2: 303-327
  13. Kulkarni, A. B., J. M. Ward, L. Yaswen, C. L. Mackall, S. R. Bauer, C. G. Huh, R. E. Gress, and S. Karlsson. 1995. Transforming growth factor-beta 1 null mice. An animal model for inflammatory disorders. Am. J. Pathol. 146: 264- 275
  14. Lawrence, D. A. 1996. Transforming growth factor-beta: A general review. Eur. Cytokine Netw. 7: 363-374
  15. Lebman, D. A., F. D. Lee, and R. L. Coffman. 1990. Mechanism for transforming growth factor beta and IL-2 enhancement of IgA expression in lipopolysaccharidestimulated B cell cultures. J. Immunol. 144: 952-959
  16. Letterio, J. J., A. G. Geiser, A. B. Kulkarni, N. S. Roche, M. B. Sporn, and A. B. Roberts. 1994. Maternal rescue of transforming growth factor-beta 1 null mice. Science 264: 1936-1938 https://doi.org/10.1126/science.8009224
  17. Lin, Y. C. and J. Stavnezer. 1992. Regulation of transcription of the germ-line Ig alpha constant region gene by an ATF element and by novel transforming growth factor-beta 1-responsive elements. J. Immunol. 149: 2914-2925
  18. Massague, J. 1990. The transforming growth factor-beta family. Annu. Rev. Cell Biol. 6: 597-641
  19. Murray, P. D., D. T. McKenzie, S. L. Swain, and M. F. Kagnoff. 1987. Interleukin 5 and interleukin 4 produced by Peyer’s patch T cells selectively enhance immunoglobulin A expression. J. Immunol. 139: 2669-2674
  20. Pakkanen, R. 1998. Determination of transforming growth factor-beta 2 (TGF-beta 2) in bovine colostrum samples. J. Immunoassay 19: 23-37
  21. Pan, Q., C. Petit-Frere, J. Stavnezer, and L. Hammarstrom. 2000. Regulation of the promoter for human immunoglobulin gamma3 germ-line transcription and its interaction with the 3’alpha enhancer. Eur. J. Immunol. 30: 1019-1029
  22. Roberts, A. B. and M. B. Sporn. 1993. Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors 8: 1-9
  23. Rogers, M. L., C. Goddard, G. O. Regester, F. J. Ballard, and D. A. Belford. 1996. Transforming growth factor beta in bovine milk: Concentration, stability and molecular mass forms. J. Endocrinol. 151: 77-86
  24. Saito, S., M. Yoshida, M. Ichijo, S. Ishizaka, and T. Tsujii. 1993. Transforming growth factor-beta (TGF-beta) in human milk. Clin. Exp. Immunol. 94: 220-224 https://doi.org/10.1111/j.1365-2249.1993.tb06004.x
  25. Sanford, L. P., I. Ormsby, A. C. Gittenberger-de Groot, H. Sariola, R. Friedman, G. P. Boivin, E. L. Cardell, and T. Doetschman. 1997. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development 124: 2659-2670
  26. Shi, M. J., S. R. Park, P. H. Kim, and J. Stavnezer. 2001. Roles of Ets proteins, NF-kappa B and nocodazole in regulating induction of transcription of mouse germline Ig alpha RNA by transforming growth factor-beta 1. Int. Immunol. 13: 733-746
  27. Shockett, P. and J. Stavnezer. 1991. Effect of cytokines on switching to IgA and alpha germline transcripts in the B lymphoma I.29 mu. Transforming growth factor-beta activates transcription of the unrearranged C alpha gene. J. Immunol. 147: 4374-4383
  28. Shull, M. M., I. Ormsby, A. B. Kier, S. Pawlowski, R. J. Diebold, M. Yin, R. Allen, C. Sidman, G. Proetzel, D. Calvin, et al. 1992. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359: 693-699
  29. Spieker-Polet, H., P. C. Yam, Z. Arbieva, S. K. Zhai, and K. L. Knight. 1999. In vitro induction of the expression of multiple IgA isotype genes in rabbit B cells by TGF-beta and IL-2. J. Immunol. 162: 5380-5388
  30. Van Obberghen-Schilling, E., P. Kondaiah, R. L. Ludwig, M. B. Sporn, and C. C. Baker. 1987. Complementary deoxyribonucleic acid cloning of bovine transforming growth factor-beta 1. Mol. Endocrinol. 1: 693-698
  31. van Vlasselaer, P., J. Punnonen, and J. E. de Vries. 1992. Transforming growth factor-beta directs IgA switching in human B cells. J. Immunol. 148: 2062-2067
  32. Xanthou, M. 1998. Immune protection of human milk. Biol. Neonate 74: 121-133
  33. Xu, R., Q. C. Doan, and G. O. Regester. 1999. Detection and characterisation of transforming growth factor-beta in porcine colostrum. Biol. Neonate 75: 59-64