scholarly journals Pro-Resolving FPR2 Agonists Regulate NADPH Oxidase-Dependent Phosphorylation of HSP27, OSR1, and MARCKS and Activation of the Respective Upstream Kinases

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 134
Author(s):  
Rosario Ammendola ◽  
Melania Parisi ◽  
Gabriella Esposito ◽  
Fabio Cattaneo
Keyword(s):  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Kinase Substrate ◽  
Peptide Receptor ◽  
Hsp 27 ◽  
Formyl Peptide ◽  
Novel Targets ◽  
Nadph Oxidase Activation

Background: Formyl peptide receptor 2 (FPR2) is involved in the pathogenesis of chronic inflammatory diseases, being activated either by pro-resolving or proinflammatory ligands. FPR2-associated signal transduction pathways result in phosphorylation of several proteins and in NADPH oxidase activation. We, herein, investigated molecular mechanisms underlying phosphorylation of heat shock protein 27 (HSP27), oxidative stress responsive kinase 1 (OSR1), and myristolated alanine-rich C-kinase substrate (MARCKS) elicited by the pro-resolving FPR2 agonists WKYMVm and annexin A1 (ANXA1). Methods: CaLu-6 cells or p22phoxCrispr/Cas9 double nickase CaLu-6 cells were incubated for 5 min with WKYMVm or ANXA1, in the presence or absence of NADPH oxidase inhibitors. Phosphorylation at specific serine residues of HSP27, OSR1, and MARCKS, as well as the respective upstream kinases activated by FPR2 stimulation was analysed. Results: Blockade of NADPH oxidase functions prevents WKYMVm- and ANXA1-induced HSP-27(Ser82), OSR1(Ser339) and MARCKS(Ser170) phosphorylation. Moreover, NADPH oxidase inhibitors prevent WKYMVm- and ANXA1-dependent activation of p38MAPK, PI3K and PKCδ, the kinases upstream to HSP-27, OSR1 and MARCKS, respectively. The same results were obtained in p22phoxCrispr/Cas9 cells. Conclusions: FPR2 shows an immunomodulatory role by regulating proinflammatory and anti-inflammatory activities and NADPH oxidase is a key regulator of inflammatory pathways. The activation of NADPH oxidase-dependent pro-resolving downstream signals suggests that FPR2 signalling and NADPH oxidase could represent novel targets for inflammation therapeutic intervention.

Neutrophil NADPH-oxidase activation by an annexin AI peptide is transduced by the formyl peptide receptor (FPR), whereas an inhibitory signal is generated independently of the FPR family receptors

2005 ◽  
Vol 78 (3) ◽  
pp. 762-771 ◽  
Author(s):  
Jennie Karlsson ◽  
Huamei Fu ◽  
François Boulay ◽  
Claes Dahlgren ◽  
Kristoffer Hellstrand ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Formyl Peptide Receptor ◽  
Peptide Receptor ◽  
Inhibitory Signal ◽  
Formyl Peptide ◽  
Nadph Oxidase Activation

The potential impacts of formyl peptide receptor 1 in inflammatory diseases

10.2741/e778 ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 436-449 ◽  
Author(s):  
Tsong-Long Hwang
Keyword(s):  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Peptide Receptor ◽  
Formyl Peptide

scholarly journals The Lipidated Peptidomimetic Lau-((S)-Aoc)-(Lys-βNphe)6-NH2Is a Novel Formyl Peptide Receptor 2 Agonist That Activates Both Human and Mouse Neutrophil NADPH Oxidase

2016 ◽  
Vol 291 (38) ◽  
pp. 19888-19899 ◽  
Author(s):  
André Holdfeldt ◽  
Sarah Line Skovbakke ◽  
Malene Winther ◽  
Michael Gabl ◽  
Christina Nielsen ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Formyl Peptide Receptor ◽  
Peptide Receptor ◽  
Formyl Peptide ◽  
Human And Mouse

scholarly journals The Antimicrobial Cathelicidin CRAMP Augments Platelet Activation during Psoriasis in Mice

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1267
Author(s):  
Maryam F. Salamah ◽  
Thomas M. Vallance ◽  
Xenia Kodji ◽  
Divyashree Ravishankar ◽  
Harry F. Williams ◽  
...  
Keyword(s):  
Psoriasis Vulgaris ◽  
Inflammatory Diseases ◽  
Platelet Reactivity ◽  
Critical Role ◽  
Disease Model ◽  
Formyl Peptide Receptor ◽  
Peptide Receptor ◽  
Fibrinogen Binding ◽  
Formyl Peptide ◽  
Inflammatory Bowel

Platelet-associated complications including thrombosis, thrombocytopenia, and haemorrhage are commonly observed during various inflammatory diseases such as psoriasis. Although several mechanisms that may contribute to the dysfunction of platelets during inflammatory diseases have been reported, knowledge on the primary molecules/mechanisms that underpin platelet-associated complications in such conditions is not fully established. Here, we report the significance of the mouse antimicrobial cathelicidin, mouse cathelicidin-related antimicrobial peptide (mCRAMP) (an orthologue of LL37 in humans), on the modulation of platelet reactivity during psoriasis using Imiquimod-induced psoriasis in mice as an inflammatory disease model for psoriasis vulgaris in humans. The activation of platelets during psoriasis is increased as evidenced by the elevated levels of fibrinogen binding and P-selectin exposure on the surface of platelets, and the level of soluble P-selectin in the plasma of psoriatic mice. The skin and plasma of psoriatic mice displayed increased levels of mCRAMP. Moreover, the plasma of psoriatic mice augmented the activation of platelets obtained from healthy mice. The effect of mCRAMP is partially mediated through formyl peptide receptor 2/3 (Fpr2/3, the orthologue to human FPR2/ALX) in platelets as a significant reduction in their activation was observed when FPR2/ALX-selective inhibitors such as WRW4 or Fpr2/3-deficient mouse platelets were used in these assays. Since the level of antimicrobial cathelicidin is increased in numerous inflammatory diseases such as psoriasis, atherosclerosis, and inflammatory bowel disease, the results of this study point towards a critical role for antimicrobial cathelicidin and FPR2/ALX in the development of platelet-related complications in such diseases.

scholarly journals Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis

2020 ◽  
Author(s):  
Martina Sundqvist ◽  
André Holdfeldt ◽  
Shane C. Wright ◽  
Thor C. Møller ◽  
Esther Siaw ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Neutrophil Migration ◽  
Adaptor Protein ◽  
Formyl Peptide Receptor ◽  
Human Neutrophils ◽  
Ros Production ◽  
Receptor Endocytosis ◽  
Formyl Peptide ◽  
Clathrin Adaptor ◽  
Nadph Oxidase Activation

AbstractFormyl peptide receptor 2 (FPR2), a member of the family of G protein-coupled receptors (GPCRs), mediates neutrophil migration, a response that has been linked to β-arrestin recruitment. β-Arrestin regulates GPCR endocytosis and can also elicit non-canonical receptor signaling. To determine the poorly understood role of β-arrestin in FPR2 endocytosis and in NADPH-oxidase activation in neutrophils, Barbadin was used as a research tool in this study. Barbadin has been shown to bind the clathrin adaptor protein (AP2) and thereby prevent β- arrestin/AP2 interaction and β-arrestin-mediated GPCR endocytosis. In agreement with this, AP2/β-arrestin interaction induced by an FPR2-specific agonist was inhibited by Barbadin. Unexpectedly, however, Barbadin did not inhibit FPR2 endocytosis, indicating that a mechanism independent of β-arrestin/AP2 interaction may sustain FPR2 endocytosis. This was confirmed by the fact, that FPR2 also underwent agonist-promoted endocytosis in β-arrestin deficient cells, albeit at a diminished level as compared to wild type cells. Dissection of the Barbadin effects on FPR2-mediated neutrophil functions including NADPH-oxidase activation mediated release of reactive oxygen species (ROS) and chemotaxis reveled that Barbadin had no effect on chemotactic migration whereas the release of ROS was potentiated/primed. The effect of Barbadin on ROS production was reversible, independent of β-arrestin recruitment, and similar to that induced by latrunculin A. Taken together, our data demonstrate that endocytic uptake of FPR2 occurs independently of β-arrestin, while Barbadin selectively augments FPR2-mediated neutrophil ROS production independently of receptor endocytosis. Given that Barbadin binds to AP2 and prevents the AP2/β-arrestin interaction, our results indicate a role for AP2 in FPR2-mediated ROS release from human neutrophils.

The potential impacts of formyl peptide receptor 1 in inflammatory diseases

10.2741/778 ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 436-449
Author(s):  
Tsong-Long Hwang
Keyword(s):  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Peptide Receptor ◽  
Formyl Peptide

scholarly journals A long-lived peptide-conjugated iridium(iii) complex as a luminescent probe and inhibitor of the cell migration mediator, formyl peptide receptor 2

2018 ◽  
Vol 9 (43) ◽  
pp. 8171-8177 ◽  
Author(s):  
Kasipandi Vellaisamy ◽  
Guodong Li ◽  
Wanhe Wang ◽  
Chung-Hang Leung ◽  
Dik-Lung Ma
Keyword(s):  
Cell Migration ◽  
Wound Repair ◽  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Luminescent Probe ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Peptide Receptor ◽  
Formyl Peptide

Formyl peptide receptors play important biological and therapeutic roles in wound repair and inflammatory diseases.

scholarly journals Stable formyl peptide receptor agonists that activate the neutrophil NADPH-oxidase identified through screening of a compound library

2011 ◽  
Vol 81 (3) ◽  
pp. 402-411 ◽  
Author(s):  
Huamei Forsman ◽  
Christina Kalderén ◽  
Anna Nordin ◽  
Erik Nordling ◽  
Annika Jernmalm Jensen ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Formyl Peptide Receptor ◽  
Compound Library ◽  
Peptide Receptor ◽  
Receptor Agonists ◽  
Formyl Peptide

scholarly journals Lipopolysaccharide-Induced Gelatinase Granule Mobilization Primes Neutrophils for Activation by Galectin-3 and Formylmethionyl-Leu-Phe

2001 ◽  
Vol 69 (2) ◽  
pp. 832-837 ◽  
Author(s):  
Jenny Almkvist ◽  
Jenny Fäldt ◽  
Claes Dahlgren ◽  
Hakon Leffler ◽  
Anna Karlsson
Keyword(s):  
Cell Surface ◽  
Nadph Oxidase ◽  
Formyl Peptide Receptor ◽  
Specific Granules ◽  
Formyl Peptide ◽  
Galectin 3 ◽  
Blood Neutrophils ◽  
A Minor ◽  
Nadph Oxidase Activation ◽  
Lps Treatment

ABSTRACT We have earlier shown that galectin-3, a lactose-binding mammalian lectin that is secreted from activated macrophages, basophils, and mast cells, induces activation of the NADPH oxidase in exudated but not in peripheral blood neutrophils (A. Karlsson, P. Follin, H. Leffler, and C. Dahlgren, Blood 91:3430–3438, 1998). The alteration in responsiveness occurring during extravasation correlated with mobilization of the gelatinase and/or specific granules to the cell surface, indicating a role for mobilizable galectin-3 receptors. In this study we have investigated galectin-3-induced NADPH oxidase activation, measured as superoxide production, in lipopolysaccharide (LPS)-primed neutrophils. Upon galectin-3 challenge, the LPS-primed cells produced superoxide, both extracellularly and intracellularly. A primed extracellular response to formylmethionyl-Leu-Phe (fMLF) was also achieved. The exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the cell surface was markedly increased after LPS treatment, indicating that granule fusion with the plasma membrane had occurred. Further assessment of specific markers for neutrophil granules showed that the LPS treatment had mobilized the gelatinase granules but only a minor fraction of the specific granules. We thus suggest that the mechanism behind LPS priming lies at the level of granule (receptor) mobilization for galectin-3 as well as for fMLF.

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