Vimentin is secreted by activated macrophages

Abstract

Vimentin is a widely expressed intermediate filament protein thought to be involved mainly in structural processes, such as wound healing. We now demonstrate that activated human macrophages secrete vimentin into the extracellular space. The maturation of blood-derived monocytes into macrophages involves several signalling pathways. We show that secretion of vimentin, which is phosphorylated at serine and threonine residues, is enhanced by the phosphatase inhibitor okadaic acid and blocked by the specific protein kinase C inhibitor GO6983. These findings are consistent with previous observations that phosphorylation of vimentin affects its intracellular localization and that vimentin is a substrate for protein kinase C (PKC). We also show that the anti-inflammatory cytokine interleukin-10 (IL-10), which inhibits PKC activity, blocks secretion of vimentin. In contrast, the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) can trigger secretion of vimentin. Finally, we found that extracellular vimentin is involved in bacterial killing and the generation of oxidative metabolites, two important functions of activated macrophages. These data establish that vimentin is secreted by macrophages in response to pro-inflammatory signalling pathways and is probably involved in immune function.

The evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep

“…Semaphorin 7A, which is expressed on activated T-cells, stimulates cytokine production in monocytes and macrophages through ITGb1, and is critical for the effector phase of the inflammatory immune response [75]. Monocyte-derived macrophages were observed to secrete vimentin (VIM) in vitro and secretion was enhanced by the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and inhibited by the anti-inflammatory cytokine IL-10 [59]. There are very few studies in the literature exploring the possibility that selection for specific PrP alleles could affect the immune response following an infection.…”

Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model

“…Picrosirius Red staining was performed for assessment of collagen deposition as described. 27 The amount of cortical fibrillary collagen was determined by observing areas stained with picrosirius red with a Zeiss Axioplan 2IE microscope. Twenty non-overlapping fields at  400 magnification from each section were analyzed in a blinded manner and quantified using a digital image analysis program (MetaMorph7.6).…”

“…Western blotting was performed as previously described. 22,30 The primary antibodies were obtained from the following sources: anti-phospho-p65 (no. 3039), anti-phospho-Smad3 (no.…”

Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore

“…Tyrosylation of vimentin was particularly pronounced after cytokine stimulation. This may be explained by the recent observation that TNF-a may trigger vimentin secretion in the extracellular space of stimulated human monocytes [47]. As indicated, secreted vimentin is phosphorylated at serine and threonine residues and acts as an anti-bacterial protein.…”