Effects of type-beta 1 transforming growth factor on the proliferation and differentiation of mouse myelomonocytic leukemia cells (M1).
Murine myelomonocytic leukemia M1 cells have been used to examine the effects of type-beta 1 transforming growth factor (TGF-beta 1) on cellular proliferation and differentiation in monocyte-macrophage lineage. TGF-beta 1 inhibited immature M1 cell growth due to a general slowdown of the cell cycle, without arrest at any specific point. Ten nanograms per milliliter TGF-beta 1 completely suppressed phagocytic activity and adhesion to the dish surface and partially inhibited the expression of Fc receptors and vimentin during the differentiation of M1 cells induced by IL-6. IL-6-induced declines in the expression of c-myc mRNA and in the accumulation of G0/G1 cells were also partially blocked by TGF-beta 1. When treated concurrently with IL-6 and TGF-beta 1, approximately 50% of M1 cells were morphologically converted to promonocyte or monocyte-like cells, which did not exhibit the characteristics of mature macrophages. Although pretreatment with TGF-beta 1 also inhibited the IL-6-induced phagocytic activity, this inhibition was reversible. Once TGF-beta 1 was removed from the culture medium after 72 h of incubation with IL-6, the kinetics of differentiation induced by IL-6 were faster in pretreated cells than in nonpretreated cells. TGF-beta 1 appears to inhibit the IL-6 induced conversion of M1 cells at the intermediate stage of monocytic differentiation.
Michishita
M
M
Division of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Hirayoshi
K
K
Tsuru
A
A
Nakamura
N
N
Yoshida
Y
Y
Okuma
M
M
Nagata
K
K
D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000378:metabolism / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D015850:Interleukin-6; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011961:Receptors, Fc; D016212:Transforming Growth Factor beta; D014746:Vimentin