Caulerpin Mitigates Helicobacter pylori-Induced Inflammation via Formyl Peptide Receptors

Int J Mol Sci. 2021 Dec 5;22(23):13154. doi: 10.3390/ijms222313154.

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.

Keywords: Helicobacter pylori; bis-indole structure; formyl peptide receptors; inflammation.

MeSH terms

  • Bacterial Proteins / immunology
  • Bacterial Proteins / pharmacology*
  • Cell Line
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / immunology*
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / immunology
  • Helicobacter pylori / metabolism*
  • Humans
  • Immunity, Innate / drug effects
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Protein Binding
  • Receptors, Formyl Peptide / chemistry
  • Receptors, Formyl Peptide / metabolism*
  • Receptors, Lipoxin / chemistry
  • Receptors, Lipoxin / metabolism*
  • Signal Transduction / drug effects
  • THP-1 Cells

Substances

  • Bacterial Proteins
  • FPR2 protein, human
  • Hp (2-20) protein, Helicobacter pylori
  • Indoles
  • Peptide Fragments
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • caulerpin