14 research outputs found
An IL-27/Stat3 axis induces expression of programmed cell death 1 ligands (PD-L1/2) on infiltrating macrophages in lymphoma
Immune escape and tolerance in the tumor microenvironment are closely involved in tumor progression, and are caused by T-cell exhaustion and mediated by the inhibitory signaling of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domaincontaining molecule-3. In the present study, we investigated the expression of the PD-1 ligand 1 (PD-L1) in a lymphoma microenvironment using paraffin-embedded tissue samples, and subsequently studied the detailed mechanism of upregulation of PD-L1 on macrophages using cultured human macrophages and lymphoma cell lines. We found that macrophages in lymphoma tissues of almost all cases of adult T-cell leukemia/lymphoma (ATLL), follicular lymphoma and diffuse large B-cell lymphoma expressed PD-L1. Cell culture studies showed that the conditioned medium of ATL-T and SLVL cell lines induced increased expression of PD-L1/2 on macrophages, and that this PD-L1/2 overexpression was dependent on activation of signal transducer and activator of transcription 3 (Stat3). In vitro studies including cytokine array analysis showed that IL-27 (heterodimer of p28 and EBI3) induced overexpression of PD-L1/2 on macrophages via Stat3 activation. Because lymphoma cell lines produced IL-27B (EBI3) but not IL-27p28, it was proposed that the IL-27p28 derived from macrophages and the IL-27B (EBI3) derived from lymphoma cells formed an IL-27 (heterodimer) that induced PD-L1/2 overexpression. Although the significance of PD-L1/2 expressions on macrophages in lymphoma progression has never been clarified, an IL-27-Stat3 axis might be a target for immunotherapy for lymphoma patients
Tomatidine, a Tomato Sapogenol, Ameliorates Hyperlipidemia and Atherosclerosis in ApoE-Deficient Mice by Inhibiting Acyl-CoA:cholesterol Acyl-transferase (ACAT)
It was previously revealed that esculeoside A, a new
glycoalkaloid,
and esculeogenin A, a new aglycon of esculeoside A, contained in ripe
tomato ameliorate atherosclerosis in apoE-deficent mice. This study
examined whether tomatidine, the aglycone of tomatine, which is a
major tomato glycoalkaloid, also shows similar inhibitory effects
on cholesterol ester (CE) accumulation in human monocyte-derived macrophages
(HMDM) and atherogenesis in apoE-deficient mice. Tomatidine significantly
inhibited the CE accumulation induced by acetylated LDL in HMDM in
a dose-dependent manner. Tomatidine also inhibited CE formation in
Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase
(ACAT)-1 or ACAT-2, suggesting that tomatidine suppresses both ACAT-1
and ACAT-2 activities. Furthermore, the oral administration of tomatidine
to apoE-deficient mice significantly reduced levels of serum cholesterol,
LDL-cholesterol, and areas of atherosclerotic lesions. The study provides
the first evidence that tomatidine significantly suppresses the activity
of ACAT and leads to reduction of atherogenesis
Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma cells is not involved in the interaction with macrophages.
Tomatidine, a Tomato Sapogenol, Ameliorates Hyperlipidemia and Atherosclerosis in ApoE-Deficient Mice by Inhibiting Acyl-CoA:cholesterol Acyl-transferase (ACAT)
It was previously revealed that esculeoside A, a new
glycoalkaloid,
and esculeogenin A, a new aglycon of esculeoside A, contained in ripe
tomato ameliorate atherosclerosis in apoE-deficent mice. This study
examined whether tomatidine, the aglycone of tomatine, which is a
major tomato glycoalkaloid, also shows similar inhibitory effects
on cholesterol ester (CE) accumulation in human monocyte-derived macrophages
(HMDM) and atherogenesis in apoE-deficient mice. Tomatidine significantly
inhibited the CE accumulation induced by acetylated LDL in HMDM in
a dose-dependent manner. Tomatidine also inhibited CE formation in
Chinese hamster ovary cells overexpressing acyl-CoA:cholesterol acyl-transferase
(ACAT)-1 or ACAT-2, suggesting that tomatidine suppresses both ACAT-1
and ACAT-2 activities. Furthermore, the oral administration of tomatidine
to apoE-deficient mice significantly reduced levels of serum cholesterol,
LDL-cholesterol, and areas of atherosclerotic lesions. The study provides
the first evidence that tomatidine significantly suppresses the activity
of ACAT and leads to reduction of atherogenesis