Lipoxin A4 Antagonizes the Mitogenic Effects of Leukotriene D4 in Human Renal Mesangial Cells

McMahon, Blaithin A.; Stenson, Catherine; McPhillips, Fiona; Fanning, Áine; Brady, Hugh R.; Godson, Catherine

doi:10.1074/jbc.m001015200

Cited by 116 publications

(107 citation statements)

References 59 publications

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“…LXA 4 /15-epi-LXA 4 through inhibition of PI3K antagonized proliferation of renal mesangial cells (53,54) and human lung fibroblasts (55). In mesangial cells, LXA 4 stimulated phosphorylation of ERK and p38 MAPK (53). However, these and the present results are not easily comparable because PMN are terminally differentiated cells that do not undergo cell division, and MAPK kinases play different roles in PMN than in proliferating cells.…”

Section: Discussioncontrasting

confidence: 80%

“…LXA 4 /15-epi-LXA 4 attenuates peroxynitrite signaling (25) via the regulation of presqualene diphosphate accumulation in human PMN (52). LXA 4 /15-epi-LXA 4 through inhibition of PI3K antagonized proliferation of renal mesangial cells (53,54) and human lung fibroblasts (55). In mesangial cells, LXA 4 stimulated phosphorylation of ERK and p38 MAPK (53).…”

Section: Discussionmentioning

confidence: 99%

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Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Kebir

József

Khreiss

et al. 2007

The Journal of Immunology

127

157

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Myeloperoxidase (MPO), a heme protein abundantly expressed in the azurophilic granules in neutrophils generates cytotoxic oxidants and signals through the adhesion molecule CD11b/CD18 (Mac‐1) to activate and rescue neutrophils from apoptosis. Since aspirin‐triggered 15‐epi‐lipoxin A4 (15‐epi‐LXA4) inhibits Mac‐1‐mediated neutrophil adhesion, we studied its impact on MPO suppression of neutrophil apoptosis. Pretreatment of neutrophils with 15‐epi‐LXA4 or its metabolically stable analog 15‐epi‐16‐p‐fluorophenoxy‐LXA4 through downregulation of surface expression of Mac‐1 and inhibition of MPO release overcame the powerful anti‐apoptosis signal from MPO. 15‐epi‐LXA4 promoted apoptosis by attenuating MPO‐induced concurrent activation of ERK and phosphatidylinositol 3‐kinase/Akt‐mediated phosphorylation of Bad and reducing the expression of the anti‐apoptotic protein Mcl‐1. These led to collapse of mitochondrial transmembrane potential, cytochrome c release, resulting in increased caspase‐3 activity. The pro‐apoptotic action of 15‐epi‐LXA4 was predominant over MPO‐mediated effects even when 15‐epi‐LXA4 was added at 4‐hour post‐MPO. 15‐epi‐LXA4 did not inhibit the catalytic activity of MPO. Our results indicate that through overriding the MPO survival signal, aspirin‐triggered lipoxins may prevent neutrophil‐mediated tissue injury. (Grant support: CIHR MOP‐64283).

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Kebir

József

Khreiss

et al. 2007

The Journal of Immunology

127

157

View full text Add to dashboard Cite

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“…The results from other groups and from ours have outlined a role for LXs as anti-inflammatory and pro-resolution mediators (Serhan et al, 1984;McMahon et al, 2000;Zhang et al, 2007;Serhan et al, 2008). Glucocorticoid-induced inhibition of phospholipase-A2 was mediated by a second messenger named lipocortin-1 or annexin-A1 (Pepinsky et al, 1986).…”

Section: Discussionmentioning

confidence: 71%

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2

et al. 2011

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Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A 4 (LXA 4 ) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA 4 , ANXA1, SAA and LL-37 were dependent on the activation of their mutual cell-surface receptor formyl peptide receptor-2 (FPR2) and subsequent ROS-MAPK-NF-kB signalings. Furthermore, our results indicated that LPS switched macrophages into an IL-10 low IL-12 high M1 profile, whereas M-CSF þ MCP-1 and FPR2 agonists skewed them into M2 (IL-10 high IL-12 low ). In that respect, through modulating the phosphorylation of signal transducer and activator of transcription-3 (STAT3), LXA 4 and ANXA1 induced monocyte differentiation into M2a þ M2c-like cells and showed antitumorigenetic activities, whereas SAA, LL-37 and M-CSF þ MCP-1 led to M2b-or M2d-like polarization, which exacerbated HCC invasion in vitro and in vivo, respectively. Our results suggest that FPR2 has an appreciable pleiotropic regulator role in tumor immunoediting.

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“…12 In the context of renal inflammation we have previously reported that human mesangial cells (hMC) express a Gprotein-coupled receptor that binds LXA 4 , known as the ALXR. 16 We have reported LXA 4 inhibition of PDGF and epidermal growth factor (EGF)-induced hMC mitogenesis. 4,6 These effects are mediated by modulation of receptor activation and inhibition of specific downstream signaling pathways, including the Akt/PKB pathway.…”

mentioning

confidence: 99%

Lipoxin A4 Modifies Platelet-Derived Growth Factor-Induced Profibrotic Gene Expression in Human Renal Mesangial Cells

Rodgers

McMahon

Mitchell

et al. 2005

The American Journal of Pathology

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Lipoxins (LXs), endogenously produced eicosanoids, possess potent anti-inflammatory, proresolution bioactivities. We investigated the potential of LXA 4 (1 to 10 nmol/L) to modify the effects of platelet-derived growth factor (PDGF)-induced gene expression in human renal mesangial cells (hMCs). Using oligonucleotide microarray analysis we profiled profibrotic cytokines and matrix-associated genes induced in response to PDGF. LXA 4 modulated the expression of many PDGF-induced genes, including transforming growth factor-␤1, fibronectin, thrombospondin, matrix metalloproteinase 1, and several collagens. Analysis of both transcript and protein levels confirmed these findings. Because the activated glomerulus is frequently a source of injurious mediators that contribute to tubulointerstitial damage, we investigated the effect of hMC-secreted products on the integrity of renal proximal tubular epithelial cells using an in vitro model of progressive renal disease. Cell supernatant from PDGF-stimulated hMCs caused morphological and genetic changes in proximal tubular epithelial cells, consistent with a profibrotic phenotype. Interestingly, supernatant from cells pre-exposed to LXA 4 and PDGF did not induce these effects. These results suggest a novel role for LXA 4

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Lipoxin A4 Antagonizes the Mitogenic Effects of Leukotriene D4 in Human Renal Mesangial Cells

Cited by 116 publications

References 59 publications

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Aspirin-Triggered Lipoxins Override the Apoptosis-Delaying Action of Serum Amyloid A in Human Neutrophils: A Novel Mechanism for Resolution of Inflammation

Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2

Lipoxin A4 Modifies Platelet-Derived Growth Factor-Induced Profibrotic Gene Expression in Human Renal Mesangial Cells

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