Kinetics and Biological Function of Transforming Growth Factor-$\beta$ Isoforms in Bovine and Human Colostrum

Abstract

Colostrum contains various kinds of cytokines including TGF-β that has potent regulatory effects on cells of the immune system. We compared the levels of TGF-β1 and TGF-β2 in bovine and human colostrum. Based on the isoform-specific ELISA, bovine colostrum collected on day 1 post-delivery retained 53.71±29.55 ng/ml of TGF-β1 and 40.41±21.78 μg/ml of TGF-β2 (n=4), while in human, 381.45± 158.24 ng/ml of TGF-β1 and 41.47±9.63 ng/ml of TGF-β2 (n=5). Thus, dominant TGF-β 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 MV 1LU cell line. Consistent with the result from the immunoassay, TGF-β1 in human and TGF-β2 in bovine colostrum were responsible for the antiproliferative 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 anti-TGF-β2 antibody or combined anti-TGF-β1/β2 antibody, but not by anti-TGF-β1 antibody alone. Similarly, TGF-β2 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-β isoforms, differentially expressed in human and bovine colostrum, may promote IgA isotype production in the neonatal intestine.