rdf:type |
|
lifeskim:mentions |
umls-concept:C0017136,
umls-concept:C0033414,
umls-concept:C0085508,
umls-concept:C0205250,
umls-concept:C0206528,
umls-concept:C0220781,
umls-concept:C0962190,
umls-concept:C1149231,
umls-concept:C1334107,
umls-concept:C1367171,
umls-concept:C1416406,
umls-concept:C1423038,
umls-concept:C1831593,
umls-concept:C1883254
|
pubmed:issue |
9
|
pubmed:dateCreated |
2007-4-19
|
pubmed:abstractText |
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.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
AIM
|
pubmed:chemical |
|
pubmed:status |
MEDLINE
|
pubmed:month |
May
|
pubmed:issn |
0022-1767
|
pubmed:author |
pubmed-author:AndreiFabioF,
pubmed-author:CaprioliFlavioF,
pubmed-author:CarusoRobertaR,
pubmed-author:Del Vecchio BlancoGiovannaG,
pubmed-author:FinaDanieleD,
pubmed-author:GROSSCC,
pubmed-author:MacDonaldThomas TTT,
pubmed-author:MonteleoneGiovanniG,
pubmed-author:PalloneFrancescoF,
pubmed-author:PaoluziOmero AlessandroOA,
pubmed-author:PelusoIlariaI,
pubmed-author:RicciVittorioV,
pubmed-author:RomanoMarcoM,
pubmed-author:StolfiCarmineC,
pubmed-author:TostiClaudioC
|
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
178
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
5957-65
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:17442980-Antibodies,
pubmed-meshheading:17442980-Cell Line,
pubmed-meshheading:17442980-Gastric Mucosa,
pubmed-meshheading:17442980-Gastritis,
pubmed-meshheading:17442980-Gelatinases,
pubmed-meshheading:17442980-Helicobacter Infections,
pubmed-meshheading:17442980-Helicobacter pylori,
pubmed-meshheading:17442980-Humans,
pubmed-meshheading:17442980-Interleukins,
pubmed-meshheading:17442980-Matrix Metalloproteinase 2,
pubmed-meshheading:17442980-Matrix Metalloproteinase 9,
pubmed-meshheading:17442980-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:17442980-NF-kappa B,
pubmed-meshheading:17442980-Receptors, Interleukin-21
|
pubmed:year |
2007
|
pubmed:articleTitle |
IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and promotes gelatinases synthesis.
|
pubmed:affiliation |
Department of Internal Medicine and Centre of Excellence for Genomic Risk Assessment in Multifactorial and Complex Diseases, University of Rome Tor Vergata, Rome, Italy.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|