Bacteria induce CTGF and CYR61 expression in epithelial cells in a lysophosphatidic acid receptor-dependent manner

Wiedmaier, Nina; Müller, Susanne; Köberle, Martin; Manncke, Birgit; Krejci, Juliane; Autenrieth, Ingo B.; Bohn, Erwin

doi:10.1016/j.ijmm.2007.06.001

Cited by 36 publications

(46 citation statements)

References 63 publications

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“…Correspondingly, Ccn1 -null mice are embryonic lethal and suffer from atrioventricular septal defects and vascular hemorrhage. In the adult, CCN1 is normally expressed at a low level in most tissues but becomes highly expressed as a result of bacterial or viral infections (12-15), or in tissue repair (16-21). Consistent with a role in injury repair, CCN1 regulates the expression of genes involved in wound healing in fibroblasts (19).…”

Section: Introductionmentioning

confidence: 99%

Matricellular Protein CCN1 Activates a Proinflammatory Genetic Program in Murine Macrophages

Bai

Chen

Lau

2010

The Journal of Immunology

150

142

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CCN1 (CYR61) is a matricellular protein that is highly expressed at sites of inflammation and wound repair. In these contexts, CCN1 can modify the activities of specific cytokines, enabling TNF-α to be cytotoxic without blocking NF-κB activity and enhancing the apoptotic activity of Fas ligand and TRAIL. In this paper, we show that CCN1 supports the adhesion of macrophages through integrin αMβ2 and syndecan-4, activates NFκB-mediated transcription, and induces a proinflammatory genetic program characteristic of classically activated M1 macrophages that participates in Th1 responses. The effects of CCN1 include upregulation of cytokines (TNF-α, IL-1α, IL-1β, IL-6, and IL-12b), chemokines (MIP-1α; MCP-3; growth-related oncogenes 1 and 2; and inflammatory protein 10), and regulators of oxidative stress and complement (inducible NO synthase and C3) and downregulation of specific receptors (TLR4 and IL-10Rβ) and anti-inflammatory factors (TGF-β1). CCN1 regulates this genetic program through at least two distinct mechanisms: an immediate-early response resulting from direct activation of NF-κB by CCN1, leading to the synthesis of cytokines including TNF-α and inflammatory protein 10; and a delayed response resulting from CCN1-induced TNF-α, which acts as an autocrine/paracrine mediator to activate the expression of other cytokines including IL-1β and IL-6. These results identify CCN1 as a novel component of the extracellular matrix that activates proinflammatory genes in macrophages, implicating its role in regulating macrophage function during inflammation.

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Section: Introductionmentioning

confidence: 99%

Matricellular Protein CCN1 Activates a Proinflammatory Genetic Program in Murine Macrophages

Bai

Chen

Lau

2010

The Journal of Immunology

150

142

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“…The possible pathway involved in the pro-fibrotic action of LPA is its capacity to increase the expression of CTGF [90]. This was observed in mesengial cells [91,92], endothelial cells [93], gingival cells [94], trabecular meshwork [95], epithelial cells [96], skeletal muscle cells [97], renal interstitial cells [49], keloid fibroblasts [98]. This involves the Rho--rhokinase (ROCK) pathway [91,99], the integrinlinked kinase [100], and may require transactivation of TGF-b-receptors as well as JNK pathway activation [101].…”

Section: Liver Fibrosismentioning

confidence: 99%

“…Moreover, a possible involvement of LPA in other fibrosis-associated diseases such in gingival fibromatosis, skin scar formation, muscular dystrophies, glaucoma and bacteria-mediated intestinal fibrosis has also been proposed [86,87,94,[96][97][98]106].…”

Section: Expert Opinion and Conclusionmentioning

confidence: 99%

Lysophosphatidic acid-1-receptor targeting agents for fibrosis

Rancoule

Pradère

Gonzalez

et al. 2011

Expert Opinion on Investigational Drugs

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“…CTGF subsequently induces collagen, fibronectin and integrin expression and induces dedifferentiation of these myoblasts [23]. This example is introducing the unambiguous link between LPA and CTGF; it has been shown that treatment of a variety of cell types with LPA induces reproducible and high level induction of CTGF [24][25][26][27][28][29][30][31][32], although not necessarily in cells directly involved in the fibrotic process. CTGF is an important profibrotic cytokine, signaling down-stream and in parallel with TGFβ [33].…”

Section: Lpa and Fibrosismentioning

confidence: 99%