title: Acquisition of secretion of transforming growth factor-beta 1 leads to autonomous suppression of scavenger receptor activity in a monocyte-macrophage cell line, THP-1.
abstract: Macrophage cells derived from the human monocytic leukemia cell line, THP-1, accumulate esterified cholesterol when cultivated in the presence of acetylated low density lipoprotein (Ac-LDL) through scavenger receptors (ScR). In the present study, we isolated a subtype of THP-1 cells that failed to accumulate esterified cholesterol when cultivated in the presence of Ac-LDL. The cells had negligible amounts of cell association and degradation of Ac-LDL compared with the parent THP-1 cells. The subtype THP-1 cells did not express ScR mRNA as well as that of lipoprotein lipase. In contrast, the expression of apolipoprotein E mRNA was greater than that found in parent THP-1 cells. The culture medium of subtype THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate inhibited the uptake of Ac-LDL and the expression of ScR in parent THP-1 cells. After a 48-h incubation in the culture medium containing 12-O-tetradecanoylphorbol-13-acetate, the culture medium of differentiated subtype THP-1 cells contained 6.9 ng/ml transforming growth factor (TGF)-beta 1, while that of parent THP-1 cells secreted below detection level, which was less than 3 ng/ml. This inhibitory effect of the conditioned medium on the expression of ScR in parent THP-1 cells was abolished by pretreatment of the culture medium with anti-TGF-beta 1 antibodies. Parent THP-1 cells expressed as much TGF-beta 1 mRNA as sTHP-1 cells after stimulation of differentiation. Although the precursor forms of TGF-beta 1 that were synthesized in both parent and subtype THP-1 cells were of similar size and were expressed at similar levels, latent TGF-beta 1-binding protein, which is necessary for the secretion of TGF-beta 1, could only be co-immunoprecipitated with anti-TGF-beta 1 antibody from subtype THP-1 cells. This suggests that subtype THP-1 cells secrete TGF-beta 1 into the medium by forming a functional complex with the latent TGF-beta 1-binding protein. We conclude that subtype THP-1 cells could not take up Ac-LDL because ScR was inhibited (leading to a loss of function) caused by the secreted TGF-beta 1.
authors.affiliation: Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Harada-Shiba
authors.forename: S
authors.initials: S
authors.lastname: Tajima
authors.forename: R
authors.initials: R
authors.lastname: Sugano
authors.forename: T
authors.initials: T
authors.lastname: Yamamura
authors.forename: Q Z
authors.initials: QZ
authors.lastname: Qiang
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D017077:Culture Media, Conditioned; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D016212:Transforming Growth Factor beta