Helicobacter pylori Hp(2-20) promotes migration and proliferation of gastric epithelial cells by interacting with formyl peptide receptors in vitro and accelerates gastric mucosal healing in vivo.
Helicobacter pylori-derived peptide RpL1 aa 2-20 (Hp(2-20)) in addition to its antimicrobial action exerts several immunomodulatory effects in eukaryotic cells by interacting with formyl peptide receptors (FPRs). It has recently been shown that activation of FPRs facilitates intestinal epithelial cell restitution. We investigated whether Hp(2-20) induces healing of injured gastric mucosa and assessed the mechanisms underlying any such effect. We investigated the expression of FPRs in two gastric epithelial cell lines (MKN-28 and AGS) at mRNA and protein level. To determine whether FPRs were functional we performed chemotaxis experiments and proliferation assays and studied the Hp(2-20)-activated downstream signaling pathway. The effect of Hp(2-20) on mucosal healing was evaluated in rats after indomethacin-induced injury. Here we show that: (1) FPRs were expressed in both cell lines; (2) Hp(2-20) stimulated migration and proliferation of gastric epithelial cells; (3) this effect was specifically mediated by formyl peptide receptor-like 1 (FPRL1) and FPRL2 and was associated with activation of FPR-related downstream signaling pathways; (4) Hp(2-20) up-regulated the expression and secretion of vascular endothelial growth factor; and (5) Hp(2-20) accelerated healing of rat gastric mucosa after injury brought about by indomethacin at both the macroscopic and microscopic levels. In conclusion, by interacting with FRPL1 and FPRL2, H. pylori-derived Hp(2-20) induces cell migration and proliferation, as well as the expression of vascular endothelial growth factor, thereby promoting gastric mucosal healing. This study provides further evidence of the complexity of the relationship between H. pylori and human gastric mucosa, and it suggests that a bacterial product may be used to heal gastric mucosal injury.
de Paulis
Amato
A
Divisione di Immunologia Clinica ed Allergologia e Centro Interdipartimentale di Ricerca di Scienze Immunologiche di Base e Cliniche, Università di Napoli Federico II, Naples, Italy. depaulis@unina.it
Prevete
Nella
N
Rossi
Francesca W
FW
Rivellese
Felice
F
Salerno
Fiamma
F
Delfino
Gabriele
G
Liccardo
Bianca
B
Avilla
Elvira
E
Montuori
Nunzia
N
Mascolo
Massimo
M
Staibano
Stefania
S
Melillo
Rosa Marina
RM
D'Argenio
Giuseppe
G
Ricci
Vittorio
V
Romano
Marco
M
Marone
Gianni
G
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology* / Q000293:injuries; D016480:Helicobacter pylori / Q000737:chemistry; D006801:Humans; D007213:Indomethacin; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
D001426:Bacterial Proteins; C433783:Hp (2-20) protein, Helicobacter pylori; D010446:Peptide Fragments; D044042:Receptors, Formyl Peptide; D007213:Indomethacin