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

被引：63

作者：

de Paulis, Amato ^{[1
,2
]}

Prevete, Nella ^{[2
]}

Rossi, Francesca W. ^{[2
]}

Rivellese, Felice ^{[2
]}

Salerno, Fiamma ^{[2
]}

Delfino, Gabriele ^{[2
]}

Liccardo, Bianca ^{[2
]}

Avilla, Elvira ^{[3
]}

Montuori, Nunzia ^{[3
]}

Mascolo, Massimo ^{[4
]}

Staibano, Stefania ^{[4
]}

Melillo, Rosa Marina ^{[3
]}

D'Argenio, Giuseppe ^{[5
]}

Ricci, Vittorio ^{[6
]}

Romano, Marco ^{[7
,8
]}

Marone, Gianni ^{[2
]}

机构：

[1] Univ Naples Federico II, Dept Clin Immunol & Allergy, Div Immunol Clin & Allergol, I-80131 Naples, Italy

[2] Univ Naples Federico II, Ctr Interdipartimentale Ric Sci Immunol Base & Cl, I-80131 Naples, Italy

[3] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy

[4] Univ Naples Federico II, Dipartimento Sci Biomorfol & Funz, Sez Patol, I-80131 Naples, Italy

[5] Univ Naples Federico II, Dipartimento Med Clin & Sperimentale, I-80131 Naples, Italy

[6] Univ Pavia, Dipartimento Fisiol, Sez Fisiol Umana, I-27100 Pavia, Italy

[7] Univ Naples 2, Dipartimento Med Chirurg Internist Clin & Sperime, Naples, Italy

[8] Univ Naples 2, Ctr Interuniv Richerche Alimenti Nutr & Apparato, Naples, Italy

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 06期

关键词：

PROTEIN-COUPLED RECEPTOR; ANTIBACTERIAL PEPTIDE; GROWTH-FACTORS; ACTIVATION; EXPRESSION; ANGIOGENESIS; CHEMOTAXIS; BASOPHILS; MECHANISM; RESPONSES;

D O I：

10.4049/jimmunol.0900863

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. The Journal of Immunology, 2009, 183: 3761-3769.

引用

页码：3761 / 3769

页数：9

共 37 条

[1] Formyl peptide receptor-1 activation enhances intestinal epithelial cell restitution through phosphatidylinositol 3-kinase-dependent activation of Rac1 and Cdc42 [J].