Therapeutic anti-inflammatory potential of formyl-peptide receptor agonists

Dufton, Neil; Perretti, Mauro

doi:10.1016/j.pharmthera.2010.04.010

Cited by 103 publications

(85 citation statements)

References 182 publications

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“…Considering the present model of CPIP induced by I/R, these founds are also in agreement with the idea that targeting ALX/FPR2 receptors in both types of cells can be useful to treat symptoms of diseases in which pathophysiology relies importantly on vascular disturbances Dufton & Perretti, 2010), specially those involving I/R-induced injuries (Gavins, 2010).…”

Section: Discussionsupporting

confidence: 91%

Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways

Piovezan

Batisti

Benevides

et al. 2017

Journal of Ethnopharmacology

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Ethnopharmacological relevanceCasearia sylvestris Sw. is widely used in popular medicine to treat conditions associated with pain. Aim of the studyThe present study investigated the influence of hydroalcoholic crude extract of Casearia sylvestris (HCE-CS) and contribution of pro-resolving mediators on mechanical hyperalgesia in a mouse model of chronic post-ischemia pain (CPIP). Methods and resultsMale Swiss mice were subjected to ischemia of the right hind paw (3 h ConclusionThese results reveal significant antihyperalgesic effect of HCE-CS on CPIP, mediated at least in part, by the pathway of resolution of inflammation centred on the axis modulated by ALX/FPR2.

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Section: Discussionsupporting

confidence: 91%

Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways

Piovezan

Batisti

Benevides

et al. 2017

Journal of Ethnopharmacology

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“…The formylated methionyl has been regarded as a key residue for the interaction of microbial peptides with the classic formyl peptide receptor (FPR1) (34,37), and it is fully logical that chemical alterations in this part of the molecule should affect the receptor-binding characteristics and by that the function of peptides that bind FPR2. With respect to the receptor involved, it is of special interest that the innate immune system senses peptide toxins through FPR2, a receptor earlier described to be primarily a target for new anti-inflammatory strategies (18,39). The structural basis for PSM␣ inactivation is not known, but other critical amino acids (besides methionine) represent possible targets for oxidative inactivation.…”

Section: Discussionmentioning

confidence: 99%

Receptor-Dependent and -Independent Immunomodulatory Effects of Phenol-Soluble Modulin Peptides from Staphylococcus aureus on Human Neutrophils Are Abrogated through Peptide Inactivation by Reactive Oxygen Species

et al. 2012

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ABSTRACTThe virulence and pathogenesis mechanisms of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) strains depend on a newly described group of phenol-soluble modulin (PSM) peptides (the PSMα peptides) with cytolytic activity. These toxins are α-helical peptides with a formyl group at the N terminus, and they activate neutrophils through formyl peptide receptor 2 (FPR2), a function closely correlated to the capacity of staphylococcal species to cause invasive infections. The effects of two synthetic PSMα peptides were investigated, and we show that they utilize FPR2 and promote neutrophils to produce reactive oxygen species (ROS) which in turn trigger inactivation of the peptides. Independently of FPR2, the PSMα peptides also downregulate the neutrophil response to other stimuli and exert a cytolytic effect to which apoptotic neutrophils are more sensitive than viable cells. The novel immunomodulatory functions of the PSMα peptides were sensitive to ROS generated by the neutrophil myeloperoxidase (MPO)-H2O2system, suggesting a role for this enzyme system in counteracting bacterial virulence.

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“…Agonists as well as antagonists for FPR2 have been suggested to be of therapeutic value [36,37], and in addition, if they in one way or another selectively stimulate/inhibit neutrophil functions, they may be used also as research tools [5]. In order to find agonists with this potency, we screened a library of small compounds and several ligands for FPR2 with varying EC 50 values were identified.…”

Section: Discussionmentioning

confidence: 99%

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

Forsman

Kalderén

Nordin

et al. 2011

Biochemical Pharmacology

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The neutrophil formyl peptide receptors (FPR1 and FPR2) are G-protein coupled receptors that can induce pro-inflammatory as well as anti-inflammatory activities when activated. Accordingly, these receptors may become therapeutic targets for the development of novel drugs to be used for reducing the inflammation induced injuries in asthma, rheumatoid arthritis, Alzheimer's disease, cardiovascular diseases and traumatic shock. We screened a library of more then 50 K small compounds for an ability of the compounds to induce a transient rise in intracellular Ca 2+ in cells transfected to express FPR2 (earlier called FPRL1 or the lipoxin A 4 receptor). Ten agonists hits were selected for further analysis representing different chemical series and five new together with five earlier described molecules were further profiled.. Compounds 1 -10 gave rise to a calcium response in the FPR2 transfectants with EC 50 values ranging from 4 x 10 -9 M to 2 x 10 -7 M. All 10 compounds activated human neutrophils to release superoxide , and based on the potency of their activity, the three most potent activators of the neutrophil NADPH-oxidase were further characterized. These three agonists were largely resistant to inactivation by neutrophil produced reactive oxygen species and shown to trigger the same functional repertoire in neutrophils as earlier described peptide agonists. Accordingly they induced chemotaxis, granule mobilization and secretion of superoxide. Interestingly, the oxidase activity was largely inhibited by cyclosporine H, an FPR1 selective antagonist, but not by PBP10, an FPR2 selective inhibitor, suggesting that FPR1 is the preferred receptor in neutrophils for all three agonists.

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Therapeutic anti-inflammatory potential of formyl-peptide receptor agonists

Cited by 103 publications

References 182 publications

Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways

Hydroalcoholic crude extract of Casearia sylvestris Sw. reduces chronic post-ischemic pain by activation of pro-resolving pathways

Receptor-Dependent and -Independent Immunomodulatory Effects of Phenol-Soluble Modulin Peptides from Staphylococcus aureus on Human Neutrophils Are Abrogated through Peptide Inactivation by Reactive Oxygen Species

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

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