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 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 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 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.

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