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Enhanced Activation of Cyclooxygenase‐2 Downregulates Th1 Signaling Pathway in Helicobacter pylori ‐infected Human Gastric Mucosa
Author(s) -
Pellicanò Antonia,
Imeneo Maria,
Leone Isabella,
Larussa Tiziana,
Luzza Francesco
Publication year - 2007
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/j.1523-5378.2007.00498.x
Subject(s) - helicobacter pylori , gastric mucosa , blot , pathogenesis , prostaglandin e , cyclooxygenase , biology , immunology , medicine , enzyme , stomach , endocrinology , gene , biochemistry
Background: Evidence suggests that an impaired T‐cell response against Helicobacter pylori plays a role in the pathogenesis of H. pylori ‐related diseases. Cyclooxygenase (COX) 2 has been shown to inhibit the production of T‐helper (Th) 1 cytokines. This study aimed to ascertain whether COX‐2 downregulates Th1 signaling pathway in human gastric mucosa colonized by H. pylori . Methods: COX‐2 expression and prostaglandin E 2 (PGE 2 ) production were determined in total proteins extracted from freshly obtained gastric biopsies of H. pylori ‐infected and uninfected patients by Western blotting and enzyme‐linked immunosorbent assay (ELISA). Phosphorylated (p)STAT4, pSTAT1, T‐bet, and pSTAT6 expression and interleukin (IL)‐12, interferon (IFN)‐γ, and IL‐4 production were also determined by Western blotting and ELISA, respectively, in total protein extracts from gastric biopsy cultures of H. pylori ‐infected patients treated without and with COX‐2 inhibitor NS‐398. Results: Enhanced expression of COX‐2 and production of PGE 2 was found in H. pylori ‐infected compared to uninfected patients. COX‐2 inhibition significantly increased expression of Th1 transcription factors along with production of IL‐12 and IFN‐γ. By contrast, no changes in the expression of STAT6 and production of IL‐4 were found. Conclusion: This study provides a mechanism by which H. pylori may actually interfere with normal T‐cell activation in human gastric mucosa, possibly enhancing its pathogenicity. The use of COX‐2 selective inhibitors as immunomodulators in the course of H. pylori infection deserves investigations.