Thrombospondin-1 differentially regulates release of IL-6 and IL-10 by human monocytic cell line U937.
We investigated possible regulatory effects of thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, on cytokine release from macrophages. Immobilized TSP-1 enhanced IL-6 release from the human monocytic U937 cells stimulated with phorbol myristate acetate and LPS, whereas it inhibited IL-10 release. The 70-kDa fragment of TSP-1 containing the type 1 repeats showed the same regulatory effects. The enhanced IL-6 release by TSP-1 was inhibited by anti-CD36 antibody or antibody against the sequence of the binding site to CD36 in the type 1 repeats of TSP-1. Conversely, the decrease in IL-10 release by TSP-1 was strengthened by the blocking of the interaction between CD36 and TSP-1. Furthermore, the involvement of TGF-beta1 in the inhibition of IL-10 release by TSP-1 was indicated by the facts that (i) TSP-1 induced activation of TGF-beta1 produced by the U937 cells, (ii) exogenously added TGF-beta1 inhibited IL-10 release, and (iii) antibody against TGF-beta1 blocked the inhibition of IL-10 release by TSP-1. Together, the present findings suggest that TSP-1 enhances IL-6 release from macrophages by interaction with CD36, whereas IL-10 release is regulated by the balance between the enhancing effect of TSP-1 via CD36 and the suppressive effect by TSP-1-activated TGF-beta1.
Yamauchi
Yasushi
Y
First Department of Biochemistry, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Kuroki
Motomu
M
Imakiire
Takayuki
T
Abe
Hironori
H
Uchida
Hiroko
H
Beppu
Richiko
R
Yamashita
Yuichi
Y
Kuroki
Masahide
M
Shirakusa
Takayuki
T
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018955:CD36 Antigens; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; C508960:TGFB1 protein, human; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D013755:Tetradecanoylphorbol Acetate