Abstract | BACKGROUND: METHODS: Expression of key actors involved in the PGD2 metabolic pathway and its receptors was analyzed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in colonic mucosal biopsies of patients from three groups: controls, quiescent and active CD patients. To determine the ability of the ENS to secrete PGD2 in proinflammatory conditions, Lipocalin-type prostaglandin D synthase (L-PGDS) expression by neurons and glial cells was analyzed by immunostaining. PGD2 levels were determined in a medium of primary culture of ENS and neuro-glial coculture model treated by lipopolysaccharide (LPS). RESULTS: In patients with active CD, inflamed colonic mucosa showed significantly higher COX2 and L-PGDS mRNA expression, and significantly higher PGD2 levels than healthy colonic mucosa. On the contrary, peroxysome proliferator-activated receptor Gamma (PPARG) expression was reduced in inflamed colonic mucosa of CD patients with active disease. Immunostaining showed that L-PGDS was expressed in the neurons of human myenteric and submucosal plexi. A rat ENS primary culture model confirmed this expression. PGD2 levels were significantly increased on primary culture of ENS treated with LPS. This production was abolished by AT-56, a specific competitive L-PGDS inhibitor. The neuro-glial coculture model revealed that each component of the ENS, ECG and neurons, could contribute to PGD2 production. CONCLUSIONS:
|
Authors | Anne-Gaelle Le Loupp, Kalyane Bach-Ngohou, Arnaud Bourreille, Hélène Boudin, Malvyne Rolli-Derkinderen, Marc G Denis, Michel Neunlist, Damien Masson |
Journal | BMC gastroenterology
(BMC Gastroenterol)
Vol. 15
Pg. 112
(Sep 04 2015)
ISSN: 1471-230X [Electronic] England |
PMID | 26338799
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cytokines
- Lipocalins
- PPAR gamma
- RNA, Messenger
- Cyclooxygenase 2
- Intramolecular Oxidoreductases
- prostaglandin R2 D-isomerase
- Prostaglandin D2
|
Topics |
- Adolescent
- Adult
- Aged
- Animals
- Cells, Cultured
- Coculture Techniques
- Crohn Disease
(metabolism, pathology)
- Cyclooxygenase 2
(genetics)
- Cytokines
(genetics)
- Enteric Nervous System
(cytology, metabolism)
- Female
- Humans
- Intestinal Mucosa
(metabolism)
- Intramolecular Oxidoreductases
(genetics, metabolism)
- Lipocalins
(genetics, metabolism)
- Male
- Middle Aged
- Myenteric Plexus
(metabolism)
- Neuroglia
(metabolism)
- Neurons
(metabolism)
- PPAR gamma
(metabolism)
- Prostaglandin D2
(genetics, metabolism)
- RNA, Messenger
(metabolism)
- Rats
- Severity of Illness Index
- Submucous Plexus
(metabolism)
- Young Adult
|