RGD Reference Report - IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis. - Rat Genome Database

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

Authors: Caruso, Roberta  Fina, Daniele  Peluso, Ilaria  Fantini, Massimo Claudio  Tosti, Claudio  Del Vecchio Blanco, Giovanna  Paoluzi, Omero Alessandro  Caprioli, Flavio  Andrei, Fabio  Stolfi, Carmine  Romano, Marco  Ricci, Vittorio  MacDonald, Thomas T  Pallone, Francesco  Monteleone, Giovanni 
Citation: Caruso R, etal., J Immunol. 2007 May 1;178(9):5957-65. doi: 10.4049/jimmunol.178.9.5957.
RGD ID: 127285542
Pubmed: PMID:17442980   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.178.9.5957   (Journal Full-text)

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-kappaB but not MAPK activation, and inhibition of NF-kappaB 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Helicobacter Infections  IEP 127285542mRNA and protein:increased expression:mucosa of stomach (human)RGD 
Helicobacter Infections  ISOIL21 (Homo sapiens)127285542; 127285542mRNA and protein:increased expression:mucosa of stomach (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il21  (interleukin 21)

Genes (Mus musculus)
Il21  (interleukin 21)

Genes (Homo sapiens)
IL21  (interleukin 21)


Additional Information