scholarly journals The N-Formyl Peptide Receptors and Rheumatoid Arthritis: A Dangerous Liaison or Confusing Relationship?

2021 ◽  
Vol 12 ◽  
Author(s):  
Ilaria Mormile ◽  
Francesca Wanda Rossi ◽  
Nella Prevete ◽  
Francescopaolo Granata ◽  
Valentina Pucino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Specific Class ◽  
Loss Of Function ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Cytokines And Chemokines ◽  
Formyl Peptide

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive symmetric inflammation of the joints resulting in bone erosion and cartilage destruction with a progressive loss of function and joint deformity. An increased number of findings support the role of innate immunity in RA: many innate immune mechanisms are responsible for producing several cytokines and chemokines involved in RA pathogenesis, such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6, and IL-1. Pattern recognition receptors (PRRs) play a crucial role in modulating the activity of the innate arm of the immune response. We focused our attention over the years on the expression and functions of a specific class of PRR, namely formyl peptide receptors (FPRs), which exert a key function in both sustaining and resolving the inflammatory response, depending on the context and/or the agonist. We performed a broad review of the data available in the literature on the role of FPRs and their ligands in RA. Furthermore, we queried a publicly available database collecting data from 90 RA patients with different clinic features to evaluate the possible association between FPRs and clinic-pathologic parameters of RA patients.

The Role of Formyl Peptide Receptors in Microbial Infection and Inflammation

2003 ◽  
Vol 2 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Yingying Le ◽  
Ronghua Sun ◽  
Guoguang Ying ◽  
Pablo Iribarren ◽  
Ji Wang
Keyword(s):  
Microbial Infection ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Infection And Inflammation

scholarly journals The Role of Collagen Triple Helix Repeat-Containing 1 Protein (CTHRC1) in Rheumatoid Arthritis

2021 ◽  
Vol 22 (5) ◽  
pp. 2426
Author(s):  
Askhat Myngbay ◽  
Limara Manarbek ◽  
Steve Ludbrook ◽  
Jeannette Kunz
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Targets ◽  
Triple Helix ◽  
Cancer Metastasis ◽  
Bone Erosion ◽  
Cartilage Destruction ◽  
Patient Treatment ◽  
Collagen Triple Helix ◽  
Potential Biomarker

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.

The Role of Formyl Peptide Receptors for Immunomodulatory Activities of Antimicrobial Peptides and Peptidomimetics

2018 ◽  
Vol 24 (10) ◽  
pp. 1100-1120 ◽  
Author(s):  
Sarah Line Skovbakke ◽  
Andre Holdfeldt ◽  
Huamei Forsman ◽  
Johan Bylund ◽  
Henrik Franzyk
Keyword(s):  
Antimicrobial Peptides ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Chemical Properties ◽  
Immunomodulatory Activity ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Natural And Synthetic

In recent years, the therapeutic potential of antimicrobial peptides (AMPs) as immunomodulators has become generally accepted. Nevertheless, only very few AMP-based compounds have progressed into clinical trials. This paradox may be explained by the fact, that some of the intrinsic properties of natural peptides, such as proteolytic and oxidative instability, render them inconvenient as therapeutics. Therefore, substantial research efforts have been dedicated to mimic the physico-chemical properties as well as biological activities of AMPs by designing and identifying more stable peptidomimetics displaying analogous immunomodulatory activity profiles. Neutrophils play key roles in host defense as major effector cells in clearance of pathogens by phagocytosis and by regulating other processes of innate immunity as well as by promoting resolution of inflammation. Several aspects of these effects are correlated to their expression of formyl peptide receptors (FPRs) that have been shown to be targets of both natural and synthetic antimicrobial peptides. In the present review recent findings highlighting the role of FPRs in mediating immunomodulatory activities of natural and synthetic AMPs as well as of stabilized peptidomimetics are discussed, and prospects for future development of immunomodulatory therapeutics are presented.

scholarly journals Annexin A1 Released in Extracellular Vesicles by Pancreatic Cancer Cells Activates Components of the Tumor Microenvironment, through Interaction with the Formyl-Peptide Receptors

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2719
Author(s):  
Nunzia Novizio ◽  
Raffaella Belvedere ◽  
Emanuela Pessolano ◽  
Alessandra Tosco ◽  
Amalia Porta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Soluble Form ◽  
Annexin A1 ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Pancreatic Cancer Cells ◽  
Formyl Peptide

Pancreatic cancer (PC) is one of the most aggressive cancers in the world. Several extracellular factors are involved in its development and metastasis to distant organs. In PC, the protein Annexin A1 (ANXA1) appears to be overexpressed and may be identified as an oncogenic factor, also because it is a component in tumor-deriving extracellular vesicles (EVs). Indeed, these microvesicles are known to nourish the tumor microenvironment. Once we evaluated the autocrine role of ANXA1-containing EVs on PC MIA PaCa-2 cells and their pro-angiogenic action, we investigated the ANXA1 paracrine effect on stromal cells like fibroblasts and endothelial ones. Concerning the analysis of fibroblasts, cell migration/invasion, cytoskeleton remodeling, and the different expression of specific protein markers, all features of the cell switching into myofibroblasts, were assessed after administration of wild type more than ANXA1 Knock-Out EVs. Interestingly, we demonstrated a mechanism by which the ANXA1-EVs complex can stimulate the activation of formyl peptide receptors (FPRs), triggering mesenchymal switches and cell motility on both fibroblasts and endothelial cells. Therefore, we highlighted the importance of ANXA1/EVs-FPR axes in PC progression as a vehicle of intercommunication tumor cells-stroma, suggesting a specific potential prognostic/diagnostic role of ANXA1, whether in soluble form or even if EVs are captured in PC.

Role of Formyl-Peptide Receptors in Chronic Rhinosinusitis

2010 ◽  
Vol 143 (2_suppl) ◽  
pp. P137-P137
Author(s):  
Amato de Paulis ◽  
Nella Prevete ◽  
Gianni Marone ◽  
Massimo Dellepiane ◽  
Renzo Mora
Keyword(s):  
Chronic Rhinosinusitis ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

Biological Role of the N-Formyl Peptide Receptors

2006 ◽  
Vol 28 (1) ◽  
pp. 103-127 ◽  
Author(s):  
M.A. Panaro ◽  
A. Acquafredda ◽  
M. Sisto ◽  
S. Lisi ◽  
A.B. Maffione ◽  
...  
Keyword(s):  
Biological Role ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

Role of Formyl Peptide Receptors in Gastrointestinal Healing

2018 ◽  
Vol 24 (18) ◽  
pp. 1966-1971 ◽  
Author(s):  
N. Prevete ◽  
A. de Paulis ◽  
D. Sgambato ◽  
R.M. Melillo ◽  
G. D`Argenio ◽  
...  
Keyword(s):  
Gi Tract ◽  
Peptide Receptors ◽  
Epithelial Repair ◽  
Formyl Peptide Receptors ◽  
Treatment Regimens ◽  
Injured Tissue ◽  
Formyl Peptide ◽  
New Treatment ◽  
Gi Mucosa

The wound healing and the barrier restoration of the gastrointestinal (GI) mucosa must be continuously ensured to allow homeostasis of the gastrointestinal tract and of all the surrounding tissues. Several lines of the evidence report a key role of innate immunity, and in particular of Pattern Recognition Receptors (PRRs), in controlling the homeostasis of GI tract by sensing commensal and pathogen bacteria, activating the immune response and regulating epithelial repair, thus guaranteeing the morphological and functional recovery of the injured tissue. We will discuss the role of a particular class of PRRs - the Formyl Peptide Receptors - in the homeostasis of GI mucosa. We here report the results of studies that strongly suggest the possibility that the activation of FPRs is crucial in the maintenance of homeostasis of the GI tract and provide indications of the potential clinical relevance of new treatment regimens involving FPR modulation for several GI disorders.

scholarly journals The Role of Formyl Peptide Receptors in Permanent and Low-Grade Inflammation: Helicobacter pylori Infection as a Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3706
Author(s):  
Paola Cuomo ◽  
Marina Papaianni ◽  
Rosanna Capparelli ◽  
Chiara Medaglia
Keyword(s):  
Helicobacter Pylori ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Formyl Peptide Receptor ◽  
Surface Pattern ◽  
Low Grade ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

Formyl peptide receptors (FPRs) are cell surface pattern recognition receptors (PRRs), belonging to the chemoattractant G protein-coupled receptors (GPCRs) family. They play a key role in the innate immune system, regulating both the initiation and the resolution of the inflammatory response. FPRs were originally identified as receptors with high binding affinity for bacteria or mitochondria N-formylated peptides. However, they can also bind a variety of structurally different ligands. Among FPRs, formyl peptide receptor-like 1 (FPRL1) is the most versatile, recognizing N-formyl peptides, non-formylated peptides, and synthetic molecules. In addition, according to the ligand nature, FPRL1 can mediate either pro- or anti-inflammatory responses. Hp(2-20), a Helicobacter pylori-derived, non-formylated peptide, is a potent FPRL1 agonist, participating in Helicobacter pylori-induced gastric inflammation, thus contributing to the related site or not-site specific diseases. The aim of this review is to provide insights into the role of FPRs in H. pylori-associated chronic inflammation, which suggests this receptor as potential target to mitigate both microbial and sterile inflammatory diseases.

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