Soluble thrombospondin-1 suppresses T cell proliferation and enhances IL-10 secretion by antigen presenting cells stimulated with phytohemagglutinin.
Thrombospondin-1 (TSP-1) is different from other components of the extracellular matrix (ECM) regarding its production and distribution. TSP-1 is considered to be released in large quantity in inflammatory sites and exogenously added TSP-1 does not bind to preformed ECM but instead binds to cells. To define the physiological role of TSP-1 in the immune system, we studied the influence of TSP-1 on the in vitro culture of T cells and antigen-presenting cells (APCs) in the presence of phytohemagglutinin. By adding soluble TSP-1 to the culture, T cell proliferation was suppressed and anti-inflammatory cytokine IL-10 secretion by APCs was enhanced. The enhanced expression of IL-10 was also demonstrated at the mRNA level by RT-PCR using multiprimer kit for cytokines. The suppression of T cell proliferation and the enhancement of IL-10 secretion with soluble TSP-1 was inhibited byadding RGDS peptide or heparin. This result indicates that the effect of soluble TSP-1 may be caused by binding to its ligand(s) on T cells and/or APCs, resulting in transducing regulatory signals to the cells or disturbing appropriate interaction between T cells and APCs. We therefore propose that TSP-1 is an immunosuppressive modulator which may play a role in inflammatory sites.
Beppu
R
R
First Department of Biochemistry, Fukuoka University School of Medicine, Japan.
Nakamura
K
K
Miyajima-Uchida
H
H
Kuroki
M
M
Khare
P D
PD
Yamauchi
Y
Y
Yamashita
Y
Y
Shirakusa
T
T
Kuroki
M
M
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D008934:Mitogens; D010835:Phytohemagglutinins; D019700:Thrombospondin 1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10