Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori

Hase, Koji; Murakami, Masamoto; Iimura, Mitsutoshi; Cole, Sheri P.; Horibe, Yoshimune; Ohtake, Takaaki; Obonyo, Marygorret; Gallo, Richard L.; Eckmann, Lars; Kagnoff, Martin F.

doi:10.1053/j.gastro.2003.08.028

Cited by 192 publications

(205 citation statements)

References 64 publications

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“…In fact, H. pylori produces other FPR ligands that may synergize with Hp(2-20) in its biological effects. Additionally, H. pylori induces the production of peptide LL37 (35). This peptide, by activating FPRs, plays an important role in wound healing (36).…”

Section: Discussionmentioning

confidence: 99%

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

Paulis¹,

Prevete²,

Rossi³

et al. 2009

The Journal of Immunology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Paulis¹,

Prevete²,

Rossi³

et al. 2009

The Journal of Immunology

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“…LL-37 is expressed along the gastrointestinal tract. For instance, LL-37 is actively produced by surface epithelial cells, as well as chief and parietal cells in the stomach [4] . The expression of LL-37 is also detectable in epithelial cells located at the surface and upper crypts of normal human colon [5] .…”

Section: Introductionmentioning

confidence: 99%

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

Wong

et al. 2010

Acta Pharmacol Sin

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Cathelicidins, a family of host defense peptides, are highly expressed during infection, inflammation and wound healing. These peptides not only have broad-spectrum antimicrobial activities, but also modulate inflammation by altering cytokine response and chemoattraction of inflammatory cells in diseased tissues. In this connection, a mouse cathelicidin has been demonstrated to prevent inflammation in the colon through enhancing mucus production and reducing production of pro-inflammatory cytokines. In addition, cathelicidins promote wound healing through stimulation of re-epithelialization and angiogenesis at injured tissues. In an animal model of gastric ulceration, the rat cathelicidin promotes ulcer healing by inducing proliferation of gastric epithelial cells both in vitro and in vivo. In conclusion, cathelicidins represent an important group of effector molecules in the innate immune system that operates a complex integration of inflammation and tissue repair in the gastrointestinal mucosa and other organs.

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“…Murine cathelicidin-related antimicrobial peptide (mCRAMP) 4 is the murine ortholog of the sole and structurally related human cathelicidin, LL-37/hCAP18 (3). In contrast to other antimicrobial peptides in the human intestinal tract, such as ␣-defensins that are restricted to small intestinal Paneth cells (4) or ␤-defensins that are expressed by crypt, villous, and surface epithelial cells throughout the small and large intestine (5), the distribution of cathelicidin in the human intestinal tract is limited to surface epithelial cells in the colon and stomach (6,7).…”

mentioning

confidence: 99%

Cathelicidin Mediates Innate Intestinal Defense against Colonization with Epithelial Adherent Bacterial Pathogens

Iimura¹,

Gallo²,

Hase³

et al. 2005

The Journal of Immunology

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199

164

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Cathelicidin-related antimicrobial peptide (mCRAMP), the sole murine cathelicidin, is encoded by the gene Cnlp. We show that mCRAMP expression in the intestinal tract is largely restricted to surface epithelial cells in the colon. Synthetic mCRAMP had antimicrobial activity against the murine enteric pathogen Citrobacter rodentium, which like the related clinically important human pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli, adheres to the apical membrane of intestinal epithelial cells. Colon epithelial cell extracts from Cnlp+/+ mice had significantly greater antimicrobial activity against C. rodentium than those of mutant Cnlp−/− mice that lack mCRAMP. Cnlp−/− mice developed significantly greater colon surface and crypt epithelial cell colonization, surface epithelial cell damage, and systemic dissemination of infection than Cnlp+/+ mice after oral infection with C. rodentium. Moreover, Cnlp+/+ mice were protected from oral infections with C. rodentium inocula that infected the majority of Cnlp−/− mice. These results establish cathelicidin as an important component of innate antimicrobial defense in the colon.

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Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori

Cited by 192 publications

References 64 publications

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 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

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

Cathelicidin Mediates Innate Intestinal Defense against Colonization with Epithelial Adherent Bacterial Pathogens

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