Integrin-dependent homotypic adhesion of neutrophils. Arachidonic acid activates Raf-1/Mek/Erk via a 5-lipoxygenase- dependent pathway.

Capodici, Constance; Pillinger, Michael H.; Han, G; Philips, Mark R.; Weissmann, Gerald

doi:10.1172/jci592

Cited by 69 publications

(65 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of this inhibition was not determined, but probably relates to the ability of E-prostanoid 2 receptors to activate adenyl cyclase, leading to cAMP accumulation, protein kinase A (PKA) activation, and ERK pathway inhibition at the level of Raf-1 interaction with 14-3-3 proteins (51)(52)(53). Consistent with such a model, E-series PGs inhibit ERK in neutrophils in a cAMP-and PKA-dependent fashion (23,54,55). In FLSCs, we have observed that the cell-permeable cAMP analog dibutyryl cAMP inhibited IL-1␤/TNF-␣-stimulated ERK activation (M.H.P.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation

Pillinger

Rosenthal

Tolani

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

We examined the regulation of matrix metalloproteinase (MMP) production by mitogen-activated protein kinases and cyclooxygenases (COXs) in fibroblast-like synoviocytes (FLSCs). IL-1β and TNF-α stimulated FLSC extracellular signal-regulated kinase (ERK) activation as well as MMP-1 and -13 release. Pharmacologic inhibitors of ERK inhibited MMP-1, but not MMP-13 expression. Whereas millimolar salicylates inhibited both ERK and MMP-1, nonsalicylate COX and selective COX-2 inhibitors enhanced stimulated MMP-1 release. Addition of exogenous PGE1 or PGE2 inhibited MMP-1, reversed the effects of COX inhibitors, and inhibited ERK activation, suggesting that COX-2 activity tonically inhibits MMP-1 production via ERK inhibition by E PGs. Exposure of FLSCs to nonselective COX and selective COX-2 inhibitors in the absence of stimulation resulted in up-regulation of MMP-1 expression in an ERK-dependent manner. Moreover, COX inhibition sufficient to reduce PGE levels increased ERK activity. Our data indicate that: 1) ERK activation mediates MMP-1 but not MMP-13 release from FLSCs, 2) COX-2-derived E PGs inhibit MMP-1 release from FLSCs via inhibition of ERK, and 3) COX inhibitors, by attenuating PGE inhibition of ERK, enhance the release of MMP-1 by FLSC.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, ERK may also be activated in response to proinflammatory stimuli (22,23). For example, Vilcek and colleagues (24 -26) have demonstrated that in FS-4 fibroblasts, ERK undergoes activation in response to the cytokines IL-1␤ and TNF-␣, both of which are critical to the pathogenesis of RA.…”

mentioning

confidence: 99%

Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation

Pillinger

Rosenthal

Tolani

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…A recent report indicates that AA, acting as a second messenger, is able to stimulate the phosphorylation and activity of ERK in a variety of cell types including human neutrophils [20]. The activation of ERK by AA through an LO-dependent but COX-independent pathway has been reported in vascular smooth muscle cells [21] and in human neutrophils [22]. The inability of BW755C, a dual inhibitor of COX and LO [23], to prevent ERK activation by fMLP in rat neutrophils ( Fig.…”

Section: Phosphorylation Of Erk Via a G Protein-dependent Andmentioning

confidence: 98%

Examination of the signal transduction pathways leading to activation of extracellular signal‐regulated kinase by formyl‐methionyl‐leucyl‐phenylalanine in rat neutrophils

Chang

Wang

1999

FEBS Letters

View full text Add to dashboard Cite

The signaling pathways leading to extracellular signal-regulated kinase (ERK) activation in formyl-methionylleucyl-phenylalanine (fMLP)-stimulated rat neutrophils were examined. fMLP-stimulated ERK activation based on immunoblot analysis with antibodies against the phosphorylation form of ERK was attenuated by the pretreatment of cells with pertussis toxin but not with a dual cyclo-oxygenase/lipoxygenase inhibitor BW755C. Exposure of cells to the tyrosine kinase inhibitor genistein, phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002, or protein kinase C (PKC) inhibitors Go «6976, Go «6983, and GF109203X inhibited fMLP-stimulated ERK phosphorylation in a concentration-dependent manner. In addition, both the phospholipase C (PLC) inhibitor U73122 and the Ca 2 chelator BAPTA attenuated ERK activation. These results indicate that G iao protein, tyrosine kinase, PI3K, PKC, and PLC/Ca 2 , but not arachidonate metabolites, act upstream of fMLP-stimulated ERK activation.z 1999 Federation of European Biochemical Societies.

show abstract

“…Oxygen-derived free radicals induce activation of ERK1/2 and a second MAP kinase, p38 in cardiac myocytes and other cells (23,24). H 2 O 2 -induced activation of ERK1/2 is mediated through the Ras/Raf-1/Mek pathway (23)(24)(25). PD098059, a selective inhibitor of ERK1/2 activation, aggravates H 2 O 2 -induced apoptosis of cardiomyocytes (23).…”

mentioning

confidence: 99%

Oxidative Damage of Cardiomyocytes Is Limited by Extracellular Regulated Kinases 1/2-mediated Induction of Cyclooxygenase-2

Adderley

Fitzgerald

1999

Journal of Biological Chemistry

346

227

View full text Add to dashboard Cite

Oxidative stress causes cardiac damage following ischemia/reperfusion and in response to anthracyclines. Extracellular signal-regulated kinases (ERK) 1/2 are activated by oxidative stress in cardiac myocytes and protect cardiac myocytes from apoptosis. Prostaglandins (PG) also protect cells from injury in a number of tissues, including the cardiomyocyte. Cyclooxygenase (COX) the rate-limiting enzyme in PG biosynthesis has two isoforms, the constitutive COX-1 and an inducible COX-2. Here, we examined the effects of two oxidative stresses, hydrogen peroxide (H 2 O 2 ) and the anthracycline doxorubicin on the activity of ERK1/2 and the expression of COX isoforms and PG formation in neonatal rat primary cardiomyocytes. These cells expressed COX-1 at rest and both COX isoforms on treatment with phorbol 12-myristate 13-acetate. Exposure to 50 M H 2 O 2 for 10 min or doxorubicin at 10 and 100 g/ml caused expression of COX-2 that was prevented by free radical scavengers. COX-2 induction was associated with activation of ERK1/2 and the specific ERK-inhibitor PD098059 abolished COX-2 expression. Treatment of cells with decoy oligonucleotides corresponding to COX-2 promoter elements implicated the AP-1 and NF-B-2 but not the NF-B-1 in the transcription of COX-2. Induction of COX-2 mRNA and protein was accompanied by increased prostacyclin formation, which was abolished by the selective COX-2 inhibitor, NS-398, and PD098059. H 2 O 2 and doxorubicin enhanced the release of lactate dehydrogenase and free radical scavengers prevented this. NS-398 enhanced the release of lactate dehydrogenase in response to H 2 O 2 and doxorubicin, whereas the injury was prevented by iloprost, a stable prostacyclin analogue. In cardiomyocytes cell injury by H 2 O 2 and doxorubicin is limited by an increase in prostacyclin formation that reflects induction of COX-2 mediated by ERK1/2 activation.

show abstract

Integrin-dependent homotypic adhesion of neutrophils. Arachidonic acid activates Raf-1/Mek/Erk via a 5-lipoxygenase- dependent pathway.

Cited by 69 publications

References 65 publications

Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation

Cyclooxygenase-2-Derived E Prostaglandins Down-Regulate Matrix Metalloproteinase-1 Expression in Fibroblast-Like Synoviocytes via Inhibition of Extracellular Signal-Regulated Kinase Activation

Examination of the signal transduction pathways leading to activation of extracellular signal‐regulated kinase by formyl‐methionyl‐leucyl‐phenylalanine in rat neutrophils

Oxidative Damage of Cardiomyocytes Is Limited by Extracellular Regulated Kinases 1/2-mediated Induction of Cyclooxygenase-2

Contact Info

Product

Resources

About