scholarly journals Caulerpin Mitigates Helicobacter pylori-Induced Inflammation via Formyl Peptide Receptors

2021 ◽  
Vol 22 (23) ◽  
pp. 13154
Author(s):  
Paola Cuomo ◽  
Chiara Medaglia ◽  
Ivana Allocca ◽  
Angela Michela Immacolata Montone ◽  
Fabrizia Guerra ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Indole Alkaloid ◽  
G Protein Coupled Receptors ◽  
Innate Immune ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
G Protein Coupled

The identification of novel strategies to control Helicobacter pylori (Hp)-associated chronic inflammation is, at present, a considerable challenge. Here, we attempt to combat this issue by modulating the innate immune response, targeting formyl peptide receptors (FPRs), G-protein coupled receptors that play key roles in both the regulation and the resolution of the innate inflammatory response. Specifically, we investigated, in vitro, whether Caulerpin—a bis-indole alkaloid isolated from algae of the genus Caulerpa—could act as a molecular antagonist scaffold of FPRs. We showed that Caulerpin significantly reduces the immune response against Hp culture filtrate, by reverting the FPR2-related signaling cascade and thus counteracting the inflammatory reaction triggered by Hp peptide Hp(2–20). Our study suggests Caulerpin to be a promising therapeutic or adjuvant agent for the attenuation of inflammation triggered by Hp infection, as well as its related adverse clinical outcomes.

scholarly journals G-protein–coupled formyl peptide receptors play a dual role in neutrophil chemotaxis and bacterial phagocytosis

2019 ◽  
Vol 30 (3) ◽  
pp. 346-356 ◽  
Author(s):  
Xi Wen ◽  
Xuehua Xu ◽  
Wenxiang Sun ◽  
Keqiang Chen ◽  
Miao Pan ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
G Protein Coupled Receptors ◽  
Peptide Receptors ◽  
Tyrosine Kinase Signaling ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
G Protein Coupled

A dogma of innate immunity is that neutrophils use G-protein–coupled receptors (GPCRs) for chemoattractant to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work showed that G-protein–coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2–/–) are defective in the phagocytosis of Escherichia coli and the chemoattractant N-formyl-Met-Leu-Phe (fMLP)-coated beads. fMLP immobilized onto the surface of a bead interacts with FPRs, which trigger a Ca2+response and induce actin polymerization to form a phagocytic cup for engulfment of the bead. This chemoattractant GPCR/Gi signaling works independently of phagocytic receptor/tyrosine kinase signaling to promote phagocytosis. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight against invading bacteria.

scholarly journals The Two Formyl Peptide Receptors Differently Regulate GPR84-Mediated Neutrophil NADPH Oxidase Activity

2021 ◽  
pp. 1-15
Author(s):  
Jonas Mårtensson ◽  
Martina Sundqvist ◽  
Asmita Manandhar ◽  
Loukas Leremias ◽  
Linjie Zhang ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Oxidase Activity ◽  
G Protein Coupled Receptors ◽  
Human Neutrophils ◽  
Peptide Receptors ◽  
Nadph Oxidase Activity ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
Specific Antagonist ◽  
G Protein Coupled

Neutrophils express the two formyl peptide receptors (FPR1 and FPR2) and the medium-chain fatty acid receptor GPR84. The FPRs are known to define a hierarchy among neutrophil G protein-coupled receptors (GPCRs), that is, the activated FPRs can either suppress or amplify GPCR responses. In this study, we investigated the position of GPR84 in the FPR-defined hierarchy regarding the activation of neutrophil nicotine adenine dinucleotide phosphate (NADPH) oxidase, an enzyme system designed to generate reactive oxygen species (ROS), which are important regulators in cell signaling and immune regulation. When resting neutrophils were activated by GPR84 agonists, a modest ROS release was induced. However, vast amounts of ROS were induced by these GPR84 agonists in FPR2-desensitized neutrophils, and the response was inhibited not only by a GPR84-specific antagonist but also by an FPR2-specific antagonist. This suggests that the amplified GPR84 agonist response is achieved through a reactivation of desensitized FPR2s. In addition, the GPR84-mediated FPR2 reactivation was independent of β-arrestin recruitment and sensitive to a protein phosphatase inhibitor. In contrast to FPR2-desensitized cells, FPR1 desensitization primarily resulted in a suppressed GPR84 agonist-induced ROS response, indicating a receptor hierarchical desensitization of GPR84 by FPR1-generated signals. In summary, our data show that the two FPRs in human neutrophils control the NADPH oxidase activity with concomitant ROS production by communicating with GPR84 through different mechanisms. While FPR1 desensitizes GPR84 and by that suppresses the release of ROS induced by GPR84 agonists, amplified ROS release is achieved by GPR84 agonists through reactivation of the desensitized FPR2.

scholarly journals Dynamic evolution of bacterial ligand recognition by formyl peptide receptors

2021 ◽  
Author(s):  
Nicole M Paterson ◽  
Hussein Al-Zubieri ◽  
Joseph Ragona ◽  
Juan Tirado ◽  
Brian V Geisbrecht ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Critical Role ◽  
Immune Defense ◽  
Innate Immune ◽  
Ligand Recognition ◽  
Immune Functions ◽  
New World Primates ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

The detection of invasive pathogens is critical for host immune defense. Cell surface receptors play a key role in the recognition of diverse microbe-associated molecules, triggering leukocyte recruitment, phagocytosis, release of antimicrobial factors, and cytokine production. The intense selective forces acting on innate immune receptor genes has led to their rapid diversification across plant and animal species. However, the impacts of this genetic variation on immune functions are often unclear. Formyl peptide receptors (FPRs) are a family of animal G-protein coupled receptors which are activated in response to a variety of ligands including formylated bacterial peptides, microbial virulence factors, and host-derived peptides. Here we investigate patterns of gene loss, sequence diversity, and ligand recognition among primate and carnivore FPRs. We observe that FPR1, which plays a critical role in innate immune defense in humans, has been lost in New World primates. Patterns of amino acid variation in FPR1 and FPR2 suggest a history of repeated positive selection acting on extracellular domains involved in ligand binding. To assess the consequences of FPR variation on bacterial ligand recognition, we measured interactions between primate FPRs and the FPR agonist Staphylococcus aureus enterotoxin B, as well as S. aureus FLIPr-like which functions as an FPR inhibitor. We find that comparatively few sequence differences between great ape FPRs are sufficient to modulate recognition of S. aureus ligands, further demonstrating how genetic variation can act to tune FPR activation in response to diverse microbial binding partners. Together this study reveals how rapid evolution of host immune receptors shapes the detection of diverse microbial molecules.

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.

scholarly journals Mesoglycan connects Syndecan‐4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro

FEBS Journal ◽  
2021 ◽  
Author(s):  
Emanuela Pessolano ◽  
Raffaella Belvedere ◽  
Nunzia Novizio ◽  
Amelia Filippelli ◽  
Mauro Perretti ◽  
...  
Keyword(s):  
Annexin A1 ◽  
Peptide Receptors ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide

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
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