Abstract
Transforming growth factor Β1 (TGFΒ1) is a regulator of cell proliferation and differentiation. Using a mouse peritoneal cell-derived mast cell culture system, we investigated the effects of TGFΒ1 on mast cell proliferation. TGFΒ1 inhibited IL-3- and IL-4-dependent connective tissue-type mast cell proliferation. The effect was concentration dependent: 50% inhibition was observed with 1.0 ng/ml TGFΒ1 and the maximal inhibitory effect (no proliferation), was observed with 10 ng/ml. Flow cytometric analysis suggested that the inhibitory effect of TGFΒ1 was due to blocking of both G1 and G2 phases. Both control and TGFΒ1-treated mast cells showed similar histamine release induced by the calcium ionophore, A23187. TGFΒ1 seems to be an important negative regulator of connective tissue-type mast cell proliferation with apparently no appreciable effect on mast cell function.
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References
Enerback L (1981) The gut mucosal mast cell. Monogr Allergy 17: 222–232
Bienenstock J, Befus AD, Pearse F, Denburg J, Goodacre R (1982) Mast cell heterogeneity: derivation and function, with emphasis on the intestine. J Allergy Clin Immunol 70: 407–412
Galli SJ, Dvorak AM, Dvorak HF (1984) Basophil and mast cell: morphologic insights into their biology, secretory patterns, and function. Prog Allergy 34: 1–141
Nakahata T, Kobayashi T, Ishiguro A, Tsuji K, Naganuma K, Ando O, Yagi Y, Tadokoro K, Akabe T (1986) Extensive proliferation of mature connective-tissue type mast cells in vitro. Nature 324: 65–67
Hamaguchi Y, Kanakura Y, Fujita J, Takeda S, Nakano T, Tarui S, Honjo T, Kitamura Y (1987) Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissue-type mast cells. J Exp Med 165: 268–273
Sporn MB, Roberts A, Wakefield LM, Benoit de Crombrugghe (1987) Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 105: 1039–1045
Derynck R, Jarrett JA, Chen EY, Goeddel DV (1986) The murine transforming growth factor-Β-precursor. J Biol Chem 261: 4377–4379
Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV (1985) Human transforming growth factor-Β-complementary DNA sequence and expression in normal and transformed cells. Nature 316: 701–705
Anzano MA, Roberts AB, Sporn MB (1986) Anchorage-independent growth of primary rat embryo cells induced by platelet-derived growth factor and inhibition by type-beta transforming growth factor. J Cell Physiol 126: 312–318
Sporn MB, Roberts AB, Wakefield LM, Assoian RK (1986) Transforming growth factor-Β: biological function and chemical structure. Science 233: 532–534
Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-Mon M, Derynck R, Sporn MB, Fauci AS (1986) Production of transforming growth factor-Β by human T lymphocyte and its potential role in the regulation of T cell growth. J Exp Med 163: 1037–1050
Ohta M, Greenberger JS, Anklesaria P, Bassols A, Massague (1987) Two transforming growth factor-Β distinguished by multipotential haematopoietic progenitor cells. Nature 329: 539–541
Greenberger JS, Sakakeeny MA, Humphries RK, Eaves CJ, Eckner RJ (1983) Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci USA 80: 2931–2935
Broide DH, Wasserman SI, Alvaro-Gracia J, Zvaifler NJ, Firestein GS (1989) Transforming growth factor-Β1 selectively inhibits IL-3 dependent mast cell proliferation without affecting mast cell function and differentiation. J Immunol 143: 1591–1597
Nakahata T, Ogawa M (1982) Identification in culture of a class of hematopoietic colony-forming units with extensive capactiy to self-renew and generate multipotential hematopoietic colonies. Proc Natl Acad Sci USA 79: 3843–3847
Moses HL, Branum EL, Proper JA, Robinson RA (1981) Transforming growth factor production by chemically transformed cells. Cancer Res 41: 2842–2848
Leof EB, Proper JA, Goustin AS, Shipley GD, DiCorleto PE, Moses HL (1986) Induction of c-sis mRNA and activity similar to platelet-derived growth factor by transforming growth factor Β: a proposed model for indirect mitogenesis involving autocrine activity. Proc Natl Acad Sci USA 83: 2453–2457
Ignotz RA, Massgue J (1986) Transforming growth factor-Β stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem 261: 4337–4345
Bascom CC, Sipes NJ, Coffey RJ, Moses HL (1989) Regulation of epithelial cell proliferation by transforming growth factors. J Cell Biochem 39: 24–32
Shipley GD, Pittelkow MR, Wille JJ, Scott RE, Moses HL (1986) Reversible inhibition of normal human prokeratinocyte proliferation by type Β transforming growth factor-growth inhibitor in serum-free medium. Cancer Res 46: 2068–2071
Roberts AB, Anzano M, Lamb LC, Smith LJ, Sporn MB (1981) New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci USA 78: 5339–5343
Moeller J, Hültner L, Schmitt E, Dörmer P (1989) Partial purification of a mast cell growth-enhancing activity and its separation from IL-3 and IL-4. J Immunol 142: 3447–3451
Frolik CA, Wakefield LM, Smith DM, Sporn MB (1984) Characterization of a membrane receptor for transforming growth factor-Β in normal rat kidney fibroblasts. J Biol Chem 259: 10995–11000
Tucker RF, Branum EL, Shipley GD, Ryan RJ, Moses HL (1984) Specific binding to cultures cells of125I-labeled type Β transforming growth factor from human platelets. Proc Natl Acad Sci USA 81: 6757–6761
Messague J, Cheifetz S, Ignotz RA, Boyd FT (1987) Multiple type-Β transforming growth factors and their receptors. J Cell Biol [Suppl] 5: 43–47
Sorensen P, Farber NM, Krystal G (1986) Identification of the interleukin-3 receptor using an iodinable, cleavable, photoreactive cross-linking agent. J Biol Chem 261: 9094–9097
Pietenpol JA, Stein RW, Moran E, Yaciuk P, Schlegel R, Lyons RM, Pittelkow MR, Münger K, Howley PM, Moses HL (1990) TGF-Β1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming protein with pRB binding domains. Cell 61: 777–785
Werness BA, Levines AJ, Howley PM (1990) Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248: 76–79
Decaprio JA, Ludlow LW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang CM, Livingston DM (1989) The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell 58: 1086–1095
Laiho M, DeCaprio JA, Ludlow JW, Livingston DM, Massague J (1990) Growth inhibition by TGFΒ linked to suppression of retinoblastoma protein phosphorylation. Cell 62: 175–185
Pietenpol JA, Holt JT, Stein RW, Moses HL (1990) Transforming growth factor Β1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. Proc Natl Acad Sci USA 87: 3758–3762
Toyota N, Kitamura Y, Ogawa K (1990) Administration of 8-methoxypsoralen and ultraviolet A irradiation (PUVA) induces turnover of mast cells in the skin of C57BL/6 mice. J Invest Dermatol 95: 353–358
Peington DW, Lopez AR, Thomas PS, Peck C, Gold WM (1992) Dog mastocytoma cells produce transforming growth factor beta. J Clin Invest 90: 35–41
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Toyota, N., Hashimoto, Y., Matsuo, S. et al. Transforming growth factor β1 inhibits IL-3- and IL-4-dependent mouse connective tissue-type mast cell proliferation. Arch Dermatol Res 287, 198–201 (1995). https://doi.org/10.1007/BF01262332
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DOI: https://doi.org/10.1007/BF01262332