CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury

Akahori, Hirokuni; Karmali, Vinit; Polavarapu, Rathnagiri; Lyle, Alicia N.; Weiss, Daiana; Shin, Eric; Husain, Ahsan; Naqvi, Nawazish; Dam, Richard Van; Habib, Anwer; Choi, Cheol Ung; King, Adrienne L.; Pachura, Kimberly; Taylor, W. Robert; Lefer, David J.; Finn, Aloke V.

doi:10.1038/ncomms8792

Cited by 82 publications

(80 citation statements)

References 39 publications

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“…Even though the direct interaction of CD163 and TWEAK does not occur in all conditions (Fick, et al, 2012), there is consistent evidence showing that TWEAK binds to CD163, and this interaction blocks other functions of TWEAK, i.e. its myogenic effects (Akahori, et al, 2015). Therefore, we speculate that in our system an interaction between CD163 and TWEAK could be promoting an anti-inflammatory macrophage phenotype.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions

et al. 2017

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M1 macrophages release pro-inflammatory factors during inflammation. They transition to an M2 phenotype and release anti-inflammatory factors to resolve inflammation. An imbalance in the transition from M1 to M2 phenotype in macrophages contributes to the development of persistent inflammation. CD163, a member of the scavenger receptor cysteine-rich family, is an M2 macrophage marker. The functional role of CD163 during the resolution of inflammation is not completely known. We postulate that CD163 contributes to the transition from M1 to M2 phenotype in macrophages. We induced CD163 gene in THP-1 and primary human macrophages using polyethylenimine nanoparticles grafted with a mannose ligand (Man-PEI). This nanoparticle specifically targets cells of monocytic origin via mannose receptors. Cells were challenged with a single or a double stimulation of lipopolysaccharide (LPS). A CD163 or empty plasmid was complexed with Man-PEI nanoparticles for cell transfections. Quantitative RT-PCR, immunocytochemistry, and ELISAs were used for molecular assessments. CD163-overexpressing macrophages displayed reduced levels of tumor necrosis factor-alpha (TNF)-α and monocytes chemoattractant protein (MCP)-1 after a single stimulation with LPS. Following a double stimulation paradigm, CD163-overexpressing macrophages showed an increase of interleukin (IL)-10 and IL-1ra, and a reduction of MCP-1. This anti-inflammatory phenotype was partially blocked by an anti-CD163 antibody (effects on IL-10 and IL-1ra). A decrease in the release of TNF-α, IL-1β, and IL-6 was observed in CD163-overexpressing human primary macrophages. The release of IL-6 was blocked by an anti-CD163 antibody in the CD163-overexpressing group. Our data show that the induction of the CD163 gene in human macrophages under inflammatory conditions produces changes in cytokine secretion in favor of an anti-inflammatory phenotype. Targeting macrophages to induce CD163 using cell-directed nanotechnology is an attractive and practical approach for inflammatory conditions that could lead to persistent pain, i.e. major surgeries, burns, rheumatoid arthritis, etc.

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Section: Discussionmentioning

confidence: 99%

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions

et al. 2017

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“…Fn14 is expressed at low levels in many tissues and cell types under physiological conditions but becomes upregulated during injury and in inflamed tissues. During acute ischemic injury, TWEAK is released from macrophages to induce satellite cell proliferation through activation of classical NF-kB and Notch signaling [82]. By contrast, TWEAK can suppress satellite cell selfrenewal through inversely modulating notch and NF-kB signaling pathways, as shown in a cardiotoxin injury model [20].…”

Section: Tnf-a In Conditions Promoting Muscle Wastingmentioning

confidence: 97%

Cytokine Signaling in Skeletal Muscle Wasting

Zhou

Liu

Liang

et al. 2016

Trends in Endocrinology & Metabolism

150

104

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“…A special focus should be on T cells and innate immune cells given the positive correlation of sPD-L1 with sCD163 (the soluble form of CD163, exclusively expressed on macrophages). 34 …”

Section: Discussionmentioning

confidence: 99%

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

et al. 2017

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Up to now, the efficacy of programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade in pancreatic cancer (PC) remains uncertain. Serum levels of soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have been reported to be independent prognostic factors in solid tumors susceptible to checkpoint blockade. Provenience, regulation and immunologic function of sPD-1 and sPD-L1 in cancer are poorly understood. To the best of our knowledge, sPD-1 and sPD-L1 have not been measured conjointly in any cancer type yet.In contrast to other tumor entities, sPD-1/sPD-L1 levels did not indicate an adverse outcome in a cohort of 41 patients with advanced PC. We observed a close positive correlation of sPD-L1 levels with sPD-1 in patients with advanced PC, suggesting a common provenience and regulation of sPD-1 and sPD-L1 in cancer patients. Higher sPD-L1 levels were present in patients with elevated C-reactive protein or strong tumoral T cell infiltration, while no correlation of sPD-L1 levels with tumoral PD-L1 expression was found. Our findings indicate that sPD-1 and sPD-L1 are markers of systemic inflammation in (pancreatic) cancer. In a subset of PC patients, elevation in sPD-L1 levels might be caused by an inflammatory tumor typeindependent of tumoral PD-L1 expression.

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CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury

Cited by 82 publications

References 39 publications

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions

Cytokine Signaling in Skeletal Muscle Wasting

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

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