Helicobacter pylori (Hp) infection is associated with gastric inflammation and ulceration. The pathways of tissue damage in Hp-infected subjects are complex, but evidence indicates that T cell-derived cytokines enhance the synthesis of matrix metalloproteinases (MMP) that contribute to mucosal ulceration and epithelial damage. In this study, we have examined the role of the T cell cytokine IL-21 in Hp-infected gastric mucosa and evaluated whether IL-21 regulates MMP production by gastric epithelial cells. We show that IL-21 is constitutively expressed in gastric mucosa and is more abundant in biopsy specimens and purified mucosal CD3(+) T cells from Hp-infected patients compared with normal patients and disease controls. We also demonstrate that IL-21R is expressed by primary gastric epithelial cells, as well as by the gastric epithelial cell lines AGS and MKN28. Consistently, AGS cells respond to IL-21 by increasing production of MMP-2 and MMP-9, but not MMP-1, MMP-3, MMP-7, or tissue inhibitors of MMP. Analysis of signaling pathways leading to MMP production reveals that IL-21 enhances NF-KB but not MAPK activation, and inhibition of NF-kappa B activation reduces IL-21-induced MMP-2 and MMP-9 production. Finally, we show that treatment of Hp-infected gastric explants with anti-IL-21 reduces epithelial cell-derived MMP-2 and MMP-9 production. These data indicate that IL-21 is overexpressed in Hp-infected gastric mucosa where it could contribute to increased epithelial gelatinase production.

Caruso, R., Fina, D., Peluso, I., Fantini, M.c., Tosti, C., Blanco, G., et al. (2007). IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. JOURNAL OF IMMUNOLOGY, 178(9), 5957-5965.

IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis

FANTINI, MASSIMO CLAUDIO;Stolfi C.;PALLONE, FRANCESCO;MONTELEONE, GIOVANNI
2007-01-01

Abstract

Helicobacter pylori (Hp) infection is associated with gastric inflammation and ulceration. The pathways of tissue damage in Hp-infected subjects are complex, but evidence indicates that T cell-derived cytokines enhance the synthesis of matrix metalloproteinases (MMP) that contribute to mucosal ulceration and epithelial damage. In this study, we have examined the role of the T cell cytokine IL-21 in Hp-infected gastric mucosa and evaluated whether IL-21 regulates MMP production by gastric epithelial cells. We show that IL-21 is constitutively expressed in gastric mucosa and is more abundant in biopsy specimens and purified mucosal CD3(+) T cells from Hp-infected patients compared with normal patients and disease controls. We also demonstrate that IL-21R is expressed by primary gastric epithelial cells, as well as by the gastric epithelial cell lines AGS and MKN28. Consistently, AGS cells respond to IL-21 by increasing production of MMP-2 and MMP-9, but not MMP-1, MMP-3, MMP-7, or tissue inhibitors of MMP. Analysis of signaling pathways leading to MMP production reveals that IL-21 enhances NF-KB but not MAPK activation, and inhibition of NF-kappa B activation reduces IL-21-induced MMP-2 and MMP-9 production. Finally, we show that treatment of Hp-infected gastric explants with anti-IL-21 reduces epithelial cell-derived MMP-2 and MMP-9 production. These data indicate that IL-21 is overexpressed in Hp-infected gastric mucosa where it could contribute to increased epithelial gelatinase production.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - GASTROENTEROLOGIA
English
CD3 antigen; cytokine; gelatinase; gelatinase A; gelatinase B; immunoglobulin enhancer binding protein; interleukin 21; interleukin 21 antibody; interleukin 21 receptor; interstitial collagenase; matrilysin; matrix metalloproteinase; mitogen activated protein kinase; reagent; stromelysin; tissue inhibitor of metalloproteinase; article; cell function; cell line; cellular distribution; clinical article; controlled study; cytokine production; enzyme synthesis; epithelium cell; gastritis; Helicobacter infection; Helicobacter pylori; human; human cell; human tissue; nonhuman; priority journal; protein expression; signal transduction; stomach biopsy; stomach mucosa; stomach ulcer; T lymphocyte; tissue culture; tissue injury; Antibodies; Cell Line; Gastric Mucosa; Gastritis; Gelatinases; Helicobacter Infections; Helicobacter pylori; Humans; Interleukins; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Receptors, Interleukin-21
PMID: 17442980
Caruso, R., Fina, D., Peluso, I., Fantini, M.c., Tosti, C., Blanco, G., et al. (2007). IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. JOURNAL OF IMMUNOLOGY, 178(9), 5957-5965.
Caruso, R; Fina, D; Peluso, I; Fantini, Mc; Tosti, C; Blanco, Gdv; Paoluzi, Oa; Caprioli, F; Andrei, F; Stolfi, C; Romano, M; Ricci, V; Macdonald, Tt; Pallone, F; Monteleone, G
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/28232
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact