Thromboxane Receptor Signaling Is Required for Fibronectin-induced Matrix Metalloproteinase 9 Production by Human and Murine Macrophages and Is Attenuated by the Arhgef1 Molecule

Hartney, John M.; Gustafson, Claire E.; Bowler, Russell P.; Pelanda, Roberta; Torres, Raul M.

doi:10.1074/jbc.m111.282772

Cited by 15 publications

(9 citation statements)

References 65 publications

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“…Intriguingly, previous studies have shown that ARHGEF1-deficient mice spontaneously develop pulmonary pathology characterized by key features of emphysema with increased expression and activity of MMPs, airspace enlargement, and decreased lung elastance (Hartney, Brown et al 2010). Of additional interest was the finding that macrophages lacking ARHGEF1 produce increased levels of MMP-2, -9 and -12 upon adhering to fibronectin (Hartney, Gustafson et al 2011) suggesting that ARHGEF1 is critical for the ability of immune cells to properly sense cues derived from the extracellular matrix, a parameter that could be of great relevance to RA pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke inhibits ROCK2 activation in T cells and modulates IL-22 production

Weng¹,

Geraghty²,

Foronjy³

et al. 2016

Molecular Immunology

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Gene-environment interactions are known to play a key role in the development of rheumatoid arthritis (RA). Exposure to cigarette smoke (CS) is one of the strongest environmental risk factors associated with RA and has been shown to mediate a range of complex immunomodulatory effects from decreased T and B cell activation to depressed phagocytic function. The effects of CS on the function of TH17 cells, one of the key TH effector subsets implicated in RA pathogenesis, are not fully understood. IRF4 is one of the crucial transcription factors involved in TH-17 differentiation and is absolutely required for the production of IL-17 and IL-21 but, interestingly, inhibits the synthesis of IL-22. The production of IL-17 and IL-21 by IRF4 can be augmented by its phosphorylation by the serine-threonine kinase ROCK2. Given that CS has been reported to increase ROCK activity in endothelial cells, here we investigated the effects of CS on the ROCK2-IRF4 axis in T cells. Surprisingly, we found that CS leads to decreased ROCK2 activation and IRF4 phosphorylation in T cells. This effect was associated with increased IL-22 production. Using a GEF pull-down assay we furthermore identify ARHGEF1 as a key upstream regulator of ROCK2 whose activity in T cells is inhibited by CS. Thus CS can inhibit the ROCK2-IRF4 axis and modulate T cell production of IL-22.

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Section: Discussionmentioning

confidence: 99%

Cigarette smoke inhibits ROCK2 activation in T cells and modulates IL-22 production

Weng¹,

Geraghty²,

Foronjy³

et al. 2016

Molecular Immunology

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“…While Fn is less active than its degradation products, it is also able to induce the expression of metalloproteinases in some contexts. In this regard, Fn increases MMP-9 production in human and murine macrophages [199]. Furthermore, Fn induces MMP-2 expression in human prostate cancer cells [200].…”

Section: Fn-fs Modulate the Upa System And Induce Mmp Expressionmentioning

confidence: 94%

Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

Pérez‐García

Carrión

Gutiérrez‐Cañas

et al. 2019

Cells

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The extracellular matrix (ECM) is a complex and specialized three-dimensional macromolecular network, present in nearly all tissues, that also interacts with cell surface receptors on joint resident cells. Changes in the composition and physical properties of the ECM lead to the development of many diseases, including osteoarthritis (OA). OA is a chronic degenerative rheumatic disease characterized by a progressive loss of synovial joint function as a consequence of the degradation of articular cartilage, also associated with alterations in the synovial membrane and subchondral bone. During OA, ECM-degrading enzymes, including urokinase-type plasminogen activator (uPA), matrix metalloproteinases (MMPs), and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs), cleave ECM components, such as fibronectin (Fn), generating fibronectin fragments (Fn-fs) with catabolic properties. In turn, Fn-fs promote activation of these proteinases, establishing a degradative and inflammatory feedback loop. Thus, the aim of this review is to update the contribution of ECM-degrading proteinases to the physiopathology of OA as well as their modulation by Fn-fs.

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“…TXA2 is synthesized in response to platelet activation by, for example, collagen-receptor glycoprotein VI (GPVI) stimulation and is an autocrine and paracrine active molecule acting as a positive-feedback mediator in platelets amplifying the initial signals to ensure the rapid activation (Li et al, 2010). The TXA2 receptor (TP) is also expressed on macrophages and monocytes where it is involved in regulation of matrix metalloproteinase 9 (Hartney et al, 2011) and tissue factor expression (Eligini et al, 2006;Gaussem et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

GPVI and Thromboxane Receptor on Platelets Promote Proinflammatory Macrophage Phenotypes during Cutaneous Inflammation

Pierre

Linke

Suo

et al. 2017

Journal of Investigative Dermatology

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Platelets are well known for their role in hemostasis but are also increasingly recognized for their supporting role in innate immune responses. Here, we studied the role of platelets in the development of peripheral inflammation and found that platelets colocalize with macrophages in the inflamed tissue outside of blood vessels in different animal models for cutaneous inflammation. Collagen-treatment of macrophages isolated from paws during zymosan-induced inflammation induced thromboxane synthesis through the platelet-expressed collagen receptor glycoprotein VI. Deletion of glycoprotein VI or its downstream effector thromboxane A2 receptor (TP) reduced zymosan-induced mechanical allodynia without altering macrophage recruitment or formation of macrophage/platelet complexes. Instead, macrophages in inflamed paws of glycoprotein VI- and TP-deficient mice exhibited an increased expression of anti-inflammatory markers and synthesized less proinflammatory mediators (prostaglandin E and IL6). TP expression on platelets was necessary to mediate increased prostaglandin E and IL6 synthesis, whereas TP expression on macrophages was sufficient to decrease the expression of the anti-inflammatory macrophage marker CD206, showing that TP activation on platelets and macrophages regulates different aspects of macrophage activation.

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Thromboxane Receptor Signaling Is Required for Fibronectin-induced Matrix Metalloproteinase 9 Production by Human and Murine Macrophages and Is Attenuated by the Arhgef1 Molecule

Abstract: Background: Arhgef1Ϫ/Ϫ macrophages exhibit exaggerated matrix metalloproteinase (MMP) 9 production when cultured

Cited by 15 publications

References 65 publications

Cigarette smoke inhibits ROCK2 activation in T cells and modulates IL-22 production

Cigarette smoke inhibits ROCK2 activation in T cells and modulates IL-22 production

Profile of Matrix-Remodeling Proteinases in Osteoarthritis: Impact of Fibronectin

GPVI and Thromboxane Receptor on Platelets Promote Proinflammatory Macrophage Phenotypes during Cutaneous Inflammation

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