Toll-like receptor 9-mediated cytosolic phospholipase A2 activation regulates expression of inducible nitric oxide synthase

Lee, Sun-Hye; Lee, Jingu; Kim, Jae‐Ryong; Baek, Suk‐Hwan

doi:10.1016/j.bbrc.2007.10.111

Cited by 12 publications

(7 citation statements)

References 22 publications

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“…TLR2 and TLR4 do not regulate C. albicans -stimulated activation of ERKs (data not shown) or AA release, but TLR2 partially mediates COX2 expression and prostanoid production (32). Because C. albicans DNA induces TLR9-dependent cytokine production, and TLR9 can mediate cPLA 2 α activation (62, 63), we compared peritoneal macrophages from wild type and TLR9 knock-out mice but found no role for TLR9 in regulating AA release, ERK activation, COX2 expression, or eicosanoid production in response to C. albicans (data not shown). Another possibility is that C. albicans stimulates production of IL-1α, IL-1β, or IL-18 that act in an autocrine manner through the IL-1 receptor to regulate responses through MyD88.…”

Section: Discussionmentioning

confidence: 99%

Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans

Suram

Gangelhoff

Taylor

et al. 2010

Journal of Biological Chemistry

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Resident tissue macrophages are activated by the fungal pathogen Candida albicans to release eicosanoids, which are important modulators of inflammation and immune responses. Our objective was to identify the macrophage receptors engaged by C. albicans that mediate activation of group IVA cytosolic phospholipase A2 (cPLA2α), a regulatory enzyme that releases arachidonic acid (AA) for production of prostaglandins and leukotrienes. A comparison of peritoneal macrophages from wild type and knock-out mice demonstrates that the β-glucan receptor Dectin-1 and MyD88 regulate early release of AA and eicosanoids in response to C. albicans. However, cyclooxygenase 2 (COX2) expression and later phase eicosanoid production are defective in MyD88−/− but not Dectin-1−/− macrophages. Furthermore, C. albicans-stimulated activation of MAPK and phosphorylation of cPLA2α on Ser-505 are regulated by MyD88 and not Dectin-1. In contrast, Dectin-1 mediates MAPK activation, cPLA2α phosphorylation, and COX2 expression in response to particulate β-glucan suggesting that other receptors engaged by C. albicans preferentially mediate these responses. Results also implicate the mannan-binding receptor Dectin-2 in regulating cPLA2α. C. albicans-stimulated MAPK activation and AA release are blocked by d-mannose and Dectin-2-specific antibody, and overexpression of Dectin-2 in RAW264.7 macrophages enhances C. albicans-stimulated MAPK activation, AA release, and COX2 expression. In addition, calcium mobilization is enhanced in RAW264.7 macrophages overexpressing Dectin-1 or -2. The results demonstrate that C. albicans engages both β-glucan and mannan-binding receptors on macrophages that act with MyD88 to regulate the activation of cPLA2α and eicosanoid production.

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Section: Discussionmentioning

confidence: 99%

Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans

Suram

Gangelhoff

Taylor

et al. 2010

Journal of Biological Chemistry

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“…Moreover, DDR2 phosphorylation was detected in injury tissues, accompanying increased collagen deposition and resulting in the production of MMPs, which mediates collagen degradation during pathophysiological events, such as skeletal formation, cellular migration, inflammation, wound healing, arthritis, and cancer [9]. MMP2/9 exhibit a unique ability to cleave the basement membranes such as collagen I [19].…”

Section: Discussionmentioning

confidence: 99%

“…DDR2 is implicated in various cancer cell behaviors such as invasion, metastasis, and angiogenesis [8]. Previous report has indicated that DDR2 activation in response to collagen I augments MMP production to degrade basement membrane during cellular migration, arthritis, and cancer [9]. Other collagen receptors, for example integrins, have been extensively studied in progression of cancers [10]; however, the role of DDR2 in metastasis and invasion of murine melanoma cells remains to be explored.…”

Section: Introductionmentioning

confidence: 99%

DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway

Poudel¹,

Lee²,

Kim³

2015

ABBS

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Metastatic melanoma is one of the most deadly and evasive cancers. Collagen I in the extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP) 2 and 9. Discoidin domain receptor (DDR) 2 is a collagen receptor that is implicated in several cancer types including breast and prostate cancers. However, the role of DDR2 in the migration and invasion of murine melanoma cells is less studied. In the present study, we investigated the effects and underlying mechanisms of DDR2 in migration and invasion of B16BL6 melanoma cells in response to collagen I. Results demonstrated that DDR2 is expressed and is phosphorylated by collagen I in the cells. Upon down-regulation of DDR2 using small-interfering RNA (siRNA) approach, both of the cell migratory and invasive phenotypes were significantly attenuated when compared with the control cells. This effect was mediated via suppression of MMP2/9 upon DDR2 inhibition. Furthermore, inhibition of DDR2 by specific siRNA markedly reduced the activation of extracellular regulated kinase (ERK) 1 and 2 and nuclear factor of kappa B (NF-κB) in the cells when compared with the control cells. Overall, these data demonstrated that DDR2 siRNA-mediated suppression of ERK1/2 and NF-κB could down-regulate the expressions of MMP2/ 9 in response to collagen I to reduce the migratory and invasive phenotypes of the cells.

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“…Overlapping and distinct patterns of pro-artherogenic responses are known to occur in monocytic cells between MCP-1, TNFalpha and PLA2 (Fuentes et al 2002). Additionally, TLR4 stimulation can activate cPLA2 and possibly sPLA2 in macrophages (Grkovich et al 2009; Ruiperez et al 2009), as does TLR9 (Lee et al 2007). In epithelial cells, endotoxin increases levels of iPLA2 via TLR4 activation (Herath et al 2009).…”

Section: Integration Of Alcohol-induced Neuroimmune Signaling Events mentioning

confidence: 99%

Neuroinflammatory Pathways in Binge Alcohol-Induced Neuronal Degeneration: Oxidative Stress Cascade Involving Aquaporin, Brain Edema, and Phospholipase A2 Activation

Collins

Neafsey

2011

Neurotox Res

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Chronic binge alcohol exposure in adult rat models causes neuronal degeneration in the cortex and hippocampus that is not reduced by excitotoxic receptor antagonists, but is prevented by antioxidants. Neuroinflammatory (glial-neuronal) signaling pathways are believed to underlie the oxidative stress and brain damage. Based on our experimental results as well as increased knowledge about the pro-neuroinflammatory potential of glial water channels, we propose that induction of aquaporin-4 can be a critical initiating factor in alcohol’s neurotoxic effects, via the instigation of cellular edema-based neuroinflammatory cascades involving increased phospholipase A2 activities, polyunsaturated fatty acid release/membrane depletion, decreased prosurvival signaling, and oxidative stress. A testable scheme for this pathway is presented that incorporates recent findings in the alcohol-brain literature indicating a role for neuroimmune activation (upregulation of NF-kappaB, proinflammatory cytokines and toll-like receptors). We present the argument that such neuroimmune activation could be associated with or even dependent on increased aquaporin-4 and glial swelling as well.

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Toll-like receptor 9-mediated cytosolic phospholipase A2 activation regulates expression of inducible nitric oxide synthase

Cited by 12 publications

References 22 publications

Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans

Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans

DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway

Neuroinflammatory Pathways in Binge Alcohol-Induced Neuronal Degeneration: Oxidative Stress Cascade Involving Aquaporin, Brain Edema, and Phospholipase A2 Activation

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Toll-like receptor 9-mediated cytosolic phospholipase A2 activation regulates expression of inducible nitric oxide synthase

Cited by 12 publications

References 22 publications

Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans

Pathways Regulating Cytosolic Phospholipase A2 Activation and Eicosanoid Production in Macrophages by Candida albicans

DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-&kappa;B pathway

Neuroinflammatory Pathways in Binge Alcohol-Induced Neuronal Degeneration: Oxidative Stress Cascade Involving Aquaporin, Brain Edema, and Phospholipase A2 Activation

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DDR2 inhibition reduces migration and invasion of murine metastatic melanoma cells by suppressing MMP2/9 expression through ERK/NF-κB pathway