Regulation of the NADPH oxidase activity and anti-microbial function of neutrophils by arachidonic acid

Hii, Charles S.; Fèrrante, Antonio

doi:10.1007/s00005-007-0014-x

Cited by 26 publications

(24 citation statements)

References 113 publications

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“…Activated PKCa phosphorylates and activates cPLA 2 (19), resulting in the release of arachidonate, which suppresses CRIg expression (14). Our studies have demonstrated that arachidonate can also stimulate cPLA 2 activity (29), most likely owing to its ability to stimulate PKCa activation (16,18), giving rise to a regulatory signaling loop (30). TNF-a, produced in response to LPS, activates cPLA 2 (31), explaining the cytokine's ability to inhibit CRIg expression.…”

Section: Discussionmentioning

confidence: 87%

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Usuwanthim

Munawara

et al. 2015

The Journal of Immunology

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The complement receptor Ig (CRIg) is selectively expressed by macrophages. This receptor not only promotes the rapid phagocytosis of bacteria by macrophages but also has anti-inflammatory and immunosuppressive functions. Previous findings have suggested that protein kinase C (PKC) may be involved in the regulation of CRIg expression in human macrophages. We have now examined the role of PKCα in CRIg expression in human monocyte-derived macrophages (MDM). Macrophages nucleofected with plasmid containing short hairpin RNA against PKCα showed markedly reduced expression of PKCα, but normal PKCζ expression, by Western blotting analysis, and vice versa. PKCα-deficient MDM showed increased expression of CRIg mRNA and protein (both the long and short form), an increase in phagocytosis of complement-opsonized Candida albicans, and decreased production of TNF-α and IL-6. TNF-α caused a marked decrease in CRIg expression, and addition of anti-TNF mAb to the TNF-α–producing MDMs increased CRIg expression. PKCα-deficient macrophages also showed significantly less bacterial LPS-induced downregulation of CRIg. In contrast, cells deficient in PKCα showed decreased expression of CR type 3 (CR3) and decreased production of TNF-α and IL-6 in response to LPS. MDM developed under conditions that increased expression of CRIg over CR3 showed significantly reduced production of TNF-α in response to opsonized C. albicans. The findings indicate that PKCα promotes the downregulation of CRIg and upregulation of CR3 expression and TNF-α and IL-6 production, a mechanism that may promote inflammation.

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Section: Discussionmentioning

confidence: 87%

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Usuwanthim

Munawara

et al. 2015

The Journal of Immunology

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“…apocynin revealed a potential value to limit peroxynitrite formation in inflammatory conditions in vivo [11]. Among others, in airways, there are some pivotal sources of superoxide radical -NADPH oxidase in inflammatory cells [41], inhibited by apocynin, mitochondrial sources [42,43] and arachidonic acid (AA) metabolism [44].…”

Section: Discussionmentioning

confidence: 99%

Apocynin decreases hydrogen peroxide and nirtate concentrations in exhaled breath in healthy subjects

Stefańska

Sokołowska

Sarniak

et al. 2010

Pulmonary Pharmacology & Therapeutics

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ARTICLE IN PRESS AbstractThe imbalance between reactive oxygen species (ROS) synthesis and antioxidants might be involved in the pathogenesis of many inflammatory diseases. NADPH oxidase, an enzyme responsible for ROS production, may represent an attractive therapeutic target to inhibit for the treatment of these diseases.Apocynin is an inhibitor of activation of NADPH oxidase complex present in the inflammatory cells.In double blind, placebo controlled, cross-over study, we investigated the effect of nebulized apocynin on ROS synthesis in 10 nonsmoking healthy volunteers. Apocynin (6 ml of 0.5 mg/ml) was administered by nebulization and its effects on H 2 O 2 , NO 2 -and NO 3 -generation were assessed after 30, 60 and 120 minutes by collecting exhaled breath condensate (EBC) samples using an EcoScreen analyzer. Additionally, respiratory parameters have been evaluated, utilizing spirometry and DLCO. We also analyzed peripheral blood differential counts and NO 2 -serum level, cough scale control and blood pressure as safety parameters. Thus, as apocynin significantly influence ROS concentration, it might have also antiinflammatory properties. As it is safe, it may have a potential to become a drug in airway inflammatory diseases treatment.

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“…Particularly, NEM has been reported to generate ROS by activation of membrane-bound NADPH oxidase which is known to exist in HepG2 cells (Ehleben et al, 1997;Cool et al, 1998). Moreover, AA is well known to have an essential role in the activation of the NADPH oxidase (Curnutte, 1985;Block et al, 2006;Hii and Ferrante, 2007;Kim et al, 2008). Thus one can easily speculate that NEM may generate ROS through activation of NADPH oxidase induced by AA released by activation of iPLA 2 in HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

Arachidonic Acid Mediates Apoptosis Induced by N-Ethylmaleimide in HepG2 Human Hepatoblastoma Cells

Lee¹

2009

Biomolecules and Therapeutics

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-We have previously reported that N-ethylmaleimide (NEM) induces apoptosis through activation of K ＋ , Cl − -cotransport (KCC) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase A 2 (PLA 2 )-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone (AACOCF3), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic PLA2 (cPLA2), the calcium-independent PLA 2 (iPLA 2 ) and the secretory PLA 2 (sPLA 2 ), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas AACOCF3 and BPB did not. NEM increased AA liberation in a dose-dependent manner, which was markedly prevented only by BEL. In addition AA by itself induced K ＋ efflux, a hallmark of KCC activation, which was comparable to that of NEM. The NEM-induced apoptosis was not significantly altered by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with AA or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, significantly induced apoptosis. Collectively, these results suggest that AA liberated through activation of iPLA2 may mediate the NEMinduced apoptosis in HepG2 cells.

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Regulation of the NADPH oxidase activity and anti-microbial function of neutrophils by arachidonic acid

Cited by 26 publications

References 113 publications

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Protein Kinase Cα Regulates the Expression of Complement Receptor Ig in Human Monocyte–Derived Macrophages

Apocynin decreases hydrogen peroxide and nirtate concentrations in exhaled breath in healthy subjects

Arachidonic Acid Mediates Apoptosis Induced by N-Ethylmaleimide in HepG2 Human Hepatoblastoma Cells

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