PI3K is involved in β1 integrin clustering by PSGL-1 and promotes β1 integrin-mediated Jurkat cell adhesion to fibronectin

Luo, Jixian; Li, Chunfeng; Xu, Tianyang; Liu, Wenai; Ba, Xueqing; Wang, Xiaoguang; Zeng, Xianlu

doi:10.1007/s11010-013-1837-x

Cited by 17 publications

(12 citation statements)

References 53 publications

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“…The isotype control antibody did not produce any significant change when compared to the pCD163 group, and it was significantly different to pCD163+anti-CD163 antibody group for IL-10 but not for IL-1ra. A weak unspecific effect of this isotype antibody has been previously observed (Luo, et al, 2014, Moura, et al, 2012). …”

Section: Resultsmentioning

confidence: 59%

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: Resultsmentioning

confidence: 59%

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

et al. 2017

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“…For example, during wound repair, MAPK activation and signalling through downstream effector proteins – MAPK3 (ERK1) and MAPK1 (ERK2) – induces stromal cell proliferation and cell motility which are required for the wounding response (Matsubayashi et al, ). Similarly, PI3K/Akt activation has also been linked with platelet signalling, an important initiator of the repair process (Guidetti et al, ) along with cell adhesion (Luo et al, ). Collectively, ECM‐mediated integrin activation and its downstream signalling pathways increase cell proliferation, survival and migration of cells (Bonnans et al, ) and thus work to establish and maintain a micro‐environment conducive to tissue repair.…”

Section: The Ecm As a Modulator Of Intracellular Signallingmentioning

confidence: 99%

The extracellular matrix as a key regulator of intracellular signalling networks

Hastings

Skhinas

Fey

et al. 2018

British J Pharmacology

172

120

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The extracellular matrix (ECM) is a salient feature of all solid tissues within the body. This complex, acellular entity is composed of hundreds of individual molecules whose assembly, architecture and biomechanical properties are critical to controlling the behaviour and phenotype of the different cell types residing within tissues. Cells are the basic unit of life and the core building block of tissues and organs. At their simplest, they follow a set of rules, governed by their genetic code and effected through the complex protein signalling networks that these genes encode. These signalling networks assimilate and process the information received by the cell to control cellular decisions that govern cell fate. The ECM is the biggest provider of external stimuli to cells and as such is responsible for influencing intracellular signalling dynamics. In this review, we discuss the inclusion of ECM as a central regulatory signalling sub-network in computational models of cellular decision making, with a focus on its role in diseases such as cancer. LINKED ARTICLES: This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc.

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“…In support of this concept, activation of mTOR was also described as downstream of PSGL-1 signaling in macrophages and induced the expression of the Rho-associated kinase-1 (ROCK-1), which suggests potential signaling through the phosphoinositide 3 kinase (PI3K) pathway [39]. Similarly on Jurkat T cells, ligation of PSGL-1 by antibody has been shown to induce β1 integrin clustering that is dependent on PI3K activation [58]. Ligation of PSGL-1 also induces cytokine secretion by macrophages, DCs, and T cells suggesting a positive role in immune regulation [38, 57, 59–61].…”

Section: Signaling By Psgl-1mentioning

confidence: 99%

PSGL-1: A New Player in the Immune Checkpoint Landscape

Tinoco

Otero

Takahashi

et al. 2017

Trends in Immunology

115

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P-selectin glycoprotein ligand-1 (PSGL-1) has long been studied as an adhesion molecule involved in immune cell trafficking and is recognized as a regulator of many facets of immune responses by myeloid cells. PSGL-1 also regulates T cell migration during homeostasis and inflammatory settings. However, recent findings indicate that PSGL-1 can also negatively regulate T cell function. As T cell differentiation is finely tuned by multiple positive and negative regulatory signals that appropriately scale the magnitude of the immune response, PSGL-1 has emerged as an important checkpoint during this process. Here we summarize what is known regarding PSGL-1 structure and function and highlight how it may act as an immune checkpoint inhibitor in T cells.

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PI3K is involved in β1 integrin clustering by PSGL-1 and promotes β1 integrin-mediated Jurkat cell adhesion to fibronectin

Cited by 17 publications

References 53 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

The extracellular matrix as a key regulator of intracellular signalling networks

PSGL-1: A New Player in the Immune Checkpoint Landscape

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