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Human follicular dendritic cells interact with T cells via expression and regulation of cyclooxygenases and prostaglandin E and I synthases
Author(s) -
Choe Jongseon,
Lee In Yong,
Cho Whajung,
Kangwon Jini Kim.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1065.7
Subject(s) - prostaglandin e , microbiology and biotechnology , prostaglandin , cyclooxygenase , germinal center , cell growth , chemistry , prostaglandin e2 receptor , biology , enzyme , biochemistry , b cell , immunology , receptor , antibody , agonist
Prostaglandin E 2 (PGE 2 ) inhibits mature T cell proliferation and protects T cells from activation‐induced cell death (AICD). We have previously demonstrated that human follicular dendritic cells (FDC) strongly express prostaglandin I synthase (PGIS). In this study, the hypothesis that FDC have regulatory roles on germinal center (GC) T cells by controlling production of PGE 2 and PGI 2 was tested. Confocal microscopic analyses of human tonsil tissues revealed that FDC indeed expressed PGE synthase (PGES) in addition to PGIS. To confirm these results, we studied the regulation mechanism of prostaglandin production in FDC, utilizing an established human FDC‐like cell line, HK. Specifically in response to TNF‐α, TGF‐β, and LPS, protein expression of cyclooxygenase (COX)‐2 and downstream PGES was up‐regulated with coordinate kinetics while COX‐1 and PGIS were constitutively expressed. The increase of these enzymes was reflected in actual production of PGE 2 and PGI 2 . Furthermore, the up‐regulation of PGE 2 and PGI 2 production was markedly down‐regulated by indomethacin and a selective COX‐2 inhibitor. PGI 2 analog and PGE 2 inhibited proliferation and AICD of T cells in dose‐ and time‐dependent manners. Finally, co‐culture experiments revealed that HK cells really inhibit proliferation and AICD of T cells. Put together, these results show an unrecognized pathway of FDC and T cell interactions and differential mechanisms for PGE 2 and PGI 2 production, suggesting an important implication for development and use of anti‐inflammatory drugs. This work was supported by the Korea Research Foundation Grant (MOEHRD, Basic Research Promotion Fund) (KRF‐2005‐041‐E00123) and the Vascular System Research Center grant from the Korea Science and Engineering Foundation.