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Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17.

Ashlin, TG; Kwan, APL; Ramji, DP; (2013) Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17. Cytokine , 64 (1) pp. 234-242. 10.1016/j.cyto.2013.06.315.

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Abstract

Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in modulating plaque stability. More recently, the ADAMTS proteases, which are known to play a key role in the control of cartilage degradation during arthritis, have been found to be expressed in atherosclerotic lesions and suggested to have potentially important functions in the control of plaque stability. Unfortunately, the action of cytokines on the expression of ADAMTS family in macrophages is poorly understood. We have investigated the effect of classical cytokines (IFN-γ and TGF-β) and those that have been recently identified (TL1A and IL-17) on the expression of ADAMTS-1, -4 and -5 in human macrophages. The expression of all three ADAMTS members was induced during differentiation of monocytes into macrophages. TGF-β had a differential action with induction of ADAMTS-1 and -5 expression and attenuation in the levels of ADAMTS-4. In contrast, IFN-γ suppressed the expression of ADAMTS-1 without having an effect on ADAMTS-4 and -5. Although TL-1A or IL-17A alone had little effect on the expression of all the members, they induced their expression synergistically when present together. These studies provide new insight into the regulation of key ADAMTS family members in human macrophages by major cytokines in relation to atherosclerosis.

Type: Article
Title: Regulation of ADAMTS-1, -4 and -5 expression in human macrophages: differential regulation by key cytokines implicated in atherosclerosis and novel synergism between TL1A and IL-17.
Location: England
DOI: 10.1016/j.cyto.2013.06.315
Keywords: ADAMTS, ADAMTS proteases, ApoB, ApoE, Atherosclerosis, Cytokines, DR3, ECM, GAPDH, Gene expression, HMDM, IFN-γ, IL, LDL, LDL receptor, LDLR, LPL, MMP, Macrophages, PMA, RT-qPCR, TGF-β, TL1A, TNF-α, VSMC, a disintegrin and metalloproteinase with thrombospondin motifs, apolipoprotein B, apolipoprotein E, death receptor 3, extracellular matrix, glyceraldehyde-3-phosphate dehydrogenase, human monocyte-derived macrophages, interferon-γ, interleukin, lipoprotein lipase, low-density lipoprotein, matrix metalloproteinase, phorbol 12-myristate 13-acetate, real-time quantitative polymerase chain reaction, transforming growth factor-β, tumour necrosis factor-like protein 1A, tumour necrosis factor-α, vascular smooth muscle cells, ADAM Proteins, ADAMTS1 Protein, ADAMTS4 Protein, ADAMTS5 Protein, Atherosclerosis, Cell Differentiation, Cell Line, Tumor, Humans, Interferon-gamma, Interleukin-17, Macrophages, Monocytes, Plaque, Atherosclerotic, Procollagen N-Endopeptidase, Transforming Growth Factor beta, Tumor Necrosis Factor Ligand Superfamily Member 15
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1406052
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