Abstract
The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or ‘M1’ phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-β1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages.
Highlights
Translocator protein (TSPO) is an 18kDa outer mitochondrial membrane protein, as yet of uncertain function, roles in steroidogenesis, apoptosis and cholesterol transport have been proposed [1]
We demonstrate a significant difference in TSPO expression between M1 phenotype macrophages activated by the M1 ‘pro-inflammatory’ stimuli, LPS and IFN-γ, and macrophages activated by M2 ‘reparative-state’ stimuli (IL-4, dexamethasone and TGFβ1)
All groups of monocyte derived macrophages (MDM) demonstrated a significant increase in TSPO expression compared to their monocyte counterparts (p
Summary
Translocator protein (TSPO) is an 18kDa outer mitochondrial membrane protein, as yet of uncertain function, roles in steroidogenesis, apoptosis and cholesterol transport have been proposed [1]. The paradigm of two opposing ends of a spectrum of macrophage phenotypes has long been established In this model, pro-inflammatory (or ‘classically activated’) macrophages are designated the term ‘M1’, having been activated by ‘M1’ stimuli, such as lipopolysaccharide (LPS) and interferon-ɣ (IFN- ɣ) [8]. Monocytes in the presence of macrophage-colony stimulating factor (M-CSF), interleukin-4 (IL-4), glucocorticoids (such as dexamethasone) or tumour growth factor-β (TGF-β), are thought to activate to an anti-inflammatory (or ‘alternatively-activated’) M2 macrophage phenotype [8,10] Such macrophages produce chemokines such as CCL17, and are associated with Th-2 cell responses [10]
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