Transforming growth factor-beta 1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation.
Transforming growth factor-beta 1 (TGF-beta 1) is an important regulator of cell growth, differentiation, and function. We show that TGF-beta 1 selectively inhibits IL-3-dependent mouse bone marrow derived mast cell (MBMMC) proliferation without affecting MBMMC function or differentiation. TGF-beta 1 significantly decreased [3H]thymidine uptake by IL-3-dependent MBMMC in a dose-dependent manner with 50% inhibition of proliferation occurring with a TGF-beta 1 concentration of 0.1 ng/ml. A brief (i.e., 30 min) incubation of MBMMC with TGF-beta 1 is sufficient to inhibit IL-3-induced proliferation of MBMMC (cultured in the absence of TGF-beta 1) for 24 to 48 h. The inhibitory effect of TGF-beta 1 on the IL-3-dependent proliferation of MBMMC is not cytotoxic as evident from the absence of MBMMC trypan blue staining, the retained functional characteristics of the MBMMC cultured in TGF-beta 1, and the reversibility of the TGF-beta 1 induced inhibition of IL-3 dependent MBMMC proliferation. MBMMC grown in TGF-beta 1 acutely (24 to 48 h) or chronically (7 to 14 days) do not exhibit functional differences in performed or newly generated mediator secretion (Ag/IgE or calcium ionophore A23187 induced MBMMC beta-hexosaminidase or leukotriene C4 release) from MBMMC grown in the absence of TGF-beta 1. In addition, MBMMC cultured for 2 wk in TGF-beta 1 do not show evidence of differentiation as assessed by cellular histamine content or Alcian blue/safranin staining. Thus, TGF-beta 1 is an important negative regulator of IL-3-dependent mast cell proliferation in vitro, selectively inhibiting IL-3-dependent MBMMC proliferation without affecting MBMMC function or differentiation.
Broide
D H
DH
Department of Medicine, University of California, San Diego 92103.
Wasserman
S I
SI
Alvaro-Gracia
J
J
Zvaifler
N J
NJ
Firestein
G S
GS
D000818:Animals; D001853:Bone Marrow; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D007377:Interleukin-3 / Q000502:physiology*; D007700:Kinetics; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013189:SRS-A / Q000096:biosynthesis; D013997:Time Factors; D015291:Transforming Growth Factors / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D006131:Growth Inhibitors; D007377:Interleukin-3; D013189:SRS-A; D015291:Transforming Growth Factors; D001619:beta-N-Acetylhexosaminidases