Prostaglandin E2, an Immunoactivator
Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn’s disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E2 is the most ubiquitously produced PG with various actions. PGE2 has been traditionally regard...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319310333 |
| _version_ | 1818962016241451008 |
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| author | Daiji Sakata Chengcan Yao Shuh Narumiya |
| author_facet | Daiji Sakata Chengcan Yao Shuh Narumiya |
| author_sort | Daiji Sakata |
| collection | DOAJ |
| description | Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn’s disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E2 is the most ubiquitously produced PG with various actions. PGE2 has been traditionally regarded as an immunosuppressant based on its inhibition of T cell activation in vitro. However, in vivo relevance of the immunosuppressant action of PGE2 has remained obscure. Recently, several groups including ourselves have made unexpected findings that PGE2 facilitates expansion of the Th17 subset of T helper cells of both human and mouse through elevation of cAMP via PGE receptors EP2 and EP4. We have further found that PGE2 can induce and not suppress Th1 differentiation under certain conditions, again, through EP2 and EP4. Given the putative roles of these Th subsets in immune diseases such as the above, these findings suggest that, on the contrary to the traditional view, PGE2 functions as a mediator of immune inflammation. Consistently, administration of an EP4 antagonist could suppress disease progression and development of antigen-specific Th17 cells in mice subjected to experimental allergic encephalomyelitis and contact hypersensitivity. In this perspective, we review these findings and discuss the prospect of EP4 antagonists as immunomodulatory drugs. Keywords:: prostaglandin (PG) E2, PGE receptor subtype, helper T cell subset, dendritic cell, immune inflammation |
| first_indexed | 2024-12-20T12:22:37Z |
| format | Article |
| id | doaj.art-30a73baed60a4a458b97bd620345a3d9 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-20T12:22:37Z |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-30a73baed60a4a458b97bd620345a3d92022-12-21T19:40:56ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-01112115Prostaglandin E2, an ImmunoactivatorDaiji Sakata0Chengcan Yao1Shuh Narumiya2Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, JapanDepartment of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, JapanDepartment of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan; Corresponding author. snaru@mfour.med.kyoto-u.ac.jpDiseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn’s disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E2 is the most ubiquitously produced PG with various actions. PGE2 has been traditionally regarded as an immunosuppressant based on its inhibition of T cell activation in vitro. However, in vivo relevance of the immunosuppressant action of PGE2 has remained obscure. Recently, several groups including ourselves have made unexpected findings that PGE2 facilitates expansion of the Th17 subset of T helper cells of both human and mouse through elevation of cAMP via PGE receptors EP2 and EP4. We have further found that PGE2 can induce and not suppress Th1 differentiation under certain conditions, again, through EP2 and EP4. Given the putative roles of these Th subsets in immune diseases such as the above, these findings suggest that, on the contrary to the traditional view, PGE2 functions as a mediator of immune inflammation. Consistently, administration of an EP4 antagonist could suppress disease progression and development of antigen-specific Th17 cells in mice subjected to experimental allergic encephalomyelitis and contact hypersensitivity. In this perspective, we review these findings and discuss the prospect of EP4 antagonists as immunomodulatory drugs. Keywords:: prostaglandin (PG) E2, PGE receptor subtype, helper T cell subset, dendritic cell, immune inflammationhttp://www.sciencedirect.com/science/article/pii/S1347861319310333 |
| spellingShingle | Daiji Sakata Chengcan Yao Shuh Narumiya Prostaglandin E2, an Immunoactivator Journal of Pharmacological Sciences |
| title | Prostaglandin E2, an Immunoactivator |
| title_full | Prostaglandin E2, an Immunoactivator |
| title_fullStr | Prostaglandin E2, an Immunoactivator |
| title_full_unstemmed | Prostaglandin E2, an Immunoactivator |
| title_short | Prostaglandin E2, an Immunoactivator |
| title_sort | prostaglandin e2 an immunoactivator |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319310333 |
| work_keys_str_mv | AT daijisakata prostaglandine2animmunoactivator AT chengcanyao prostaglandine2animmunoactivator AT shuhnarumiya prostaglandine2animmunoactivator |