Recombinant human transforming growth factor - β belongs to a recently discovered TGF - β superfamily that regulates cell growth and differentiation. In addition to TGF - β, this family also includes activators, inhibitors, Mullerian inhibitor substance (MIS), and bone morphogenetic proteins (BMPs).
At first, research on the biological functions of TGF - β mainly focused on inflammation, tissue repair, and embryonic development. It was found that TGF - β has important regulatory effects on cell growth, differentiation, and immune function. TGF - β 1, β 2, and β 3 have similar functions. Generally speaking, TGF - β stimulates cells of mesenchymal origin while inhibiting cells of epithelial or neuroectodermal origin.
(1) Inhibiting the proliferation of immune active cells: ① Inhibiting the colony formation of mouse hematopoietic precursor cells and LTBMC induced by IL-3, GM-CSF, M-CSF, and reducing the responsiveness of megakaryocytes to IL-3T and CSF. ② Inhibit thymocyte proliferation induced by ConA or ConA in combination with IL-2 and IL-6. ③ Inhibit T cell proliferation stimulated by mitogens, allogeneic antigens, or IL-2 dependent T cell growth. ④ Inhibition of IL-2 dependent B cell proliferation after SAC stimulation.
(2) Regulation of cell phenotype: ① Inhibition of IL-2R, TfR, and TLiSA1 activation antigen expression induced by IL-2 in T cells, with no effect on CD3 expression. ② Inhibit IFN - γ - induced MHC class II antigen expression in melanoma cells.
(3) Inhibiting lymphocyte differentiation: ① Inhibiting IL-2 and BCDF dependent B cell secretion of IgM, promoting B cell secretion of Ig type conversion to IgA and IgE. ② Inhibition of CTL, NK, and LAK functions in mixed lymphocyte culture (MLC) can be reversed by TNF - α (mouse MIC) or IL-2 (human MLC). ③ Inhibit NK activity in PBMCs and the response of NK cells to TNF - α. ④ Inhibition of ConA and IL-2, IL-6 synergistically induce the activity of MHC unrestricted killer cells in mouse thymus.
(4) Inhibition of cytokine production: such as inhibiting the production of IFN - γ and TNF - α in PBMCs.
(5) Other regulatory effects: ① Promote the growth of fibroblasts, osteoblasts, and Schwann cells. TGF - β 1 and TGF - β 2 promote the production of IL-6 in human fibroblasts, and their mechanism may be through the regulation of IL-6 gene transcription. ② Inhibit the growth of epithelial cells, osteoclasts, endothelial cells, and the formation of fat, myocardium, and skeletal muscle. TGF - β can antagonize certain biological functions of EGF. ③ Promoting the expression of extracellular matrix (ECM) such as collagen and fibronectin and inhibiting ECM degradation play an important role in the process of cell morphogenesis, proliferation, and differentiation, which is beneficial for embryonic development and cell repair. Animal in vivo experiments have shown that local injection of TGF - β can promote wound healing and typical granulation tissue formation. ④ Chemoattractant for monocytes and fibroblasts, but does not cause the production of gelatinous particles and oxides. ⑤ Inhibit the adhesion between lymphocytes and endothelial cells. ⑥ Promote the release of histamine from eosinophils.
(6) TGF - β 1 and oncogene expression: TGF - β 1 can induce the expression of c-sis, but inhibit the expression of c-myc. This induction or inhibition effect is related to the type of cells involved and the different functions of TGF - β. TGF - β induces c-sis gene expression in fibroblasts, which is related to promoting their growth in soft agar; The inhibition of epithelial keratinocyte growth is related to the inhibition of the expression of the c-myc gene. TGF - β 1, TGF - β 2, and TGF - β 3 are very similar in most biological functions, but there may be significant differences in some functions, such as the growth inhibitory effect of TGF - β 2 on vascular endothelial cells and hematopoietic progenitor cells being only 1% of that of TGF - β 1 and TGF - β 3.