ABSTRACT
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.
Subject(s)
Bacterial Proteins/pharmacology , Helicobacter Infections/immunology , Helicobacter pylori/metabolism , Indoles/pharmacology , Peptide Fragments/pharmacology , Receptors, Formyl Peptide/metabolism , Receptors, Lipoxin/metabolism , Bacterial Proteins/immunology , Cell Line , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Helicobacter pylori/immunology , Humans , Immunity, Innate/drug effects , Indoles/chemistry , Models, Molecular , Peptide Fragments/immunology , Protein Binding , Receptors, Formyl Peptide/chemistry , Receptors, Lipoxin/chemistry , Signal Transduction/drug effects , THP-1 CellsABSTRACT
Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people's lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30-50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.
