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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sturm, EM; Radnai, B; Jandl, K; Stančić, A; Parzmair, GP; Högenauer, C; Kump, P; Wenzl, H; Petritsch, W; Pieber, TR; Schuligoi, R; Marsche, G; Ferreirós, N; Heinemann, A; Schicho, R.
Opposing roles of prostaglandin D2 receptors in ulcerative colitis.
J Immunol. 2014; 193(2):827-839
Doi: 10.4049/jimmunol.1303484
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- Führende Autor*innen der Med Uni Graz
- Böhm Eva
- Schicho Rudolf
- Co-Autor*innen der Med Uni Graz
- Constantini-Kump Patrizia
- Heinemann Akos
- Hoegenauer Christoph
- Jandl Katharina
- Marsche Gunther
- Parzmair Gerald Peter
- Petritsch Wolfgang
- Pieber Thomas
- Radnai Balazs
- Schuligoi Rufina
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- Abstract:
- Proresolution functions were reported for PGD2 in colitis, but the role of its two receptors, D-type prostanoid (DP) and, in particular, chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2), is less well defined. We investigated DP and CRTH2 expression and function during human and murine ulcerative colitis (UC). Expression of receptors was measured by flow cytometry on peripheral blood leukocytes and by immunohistochemistry and immunoblotting in colon biopsies of patients with active UC and healthy individuals. Receptor involvement in UC was evaluated in a mouse model of dextran sulfate sodium colitis. DP and CRTH2 expression changed in leukocytes of patients with active UC in a differential manner. In UC patients, DP showed higher expression in neutrophils but lower in monocytes as compared with control subjects. In contrast, CRTH2 was decreased in eosinophils, NK, and CD3(+) T cells but not in monocytes and CD3(+)/CD4(+) T cells. The decrease of CRTH2 on blood eosinophils clearly correlated with disease activity. DP correlated positively with disease activity in eosinophils but inversely in neutrophils. CRTH2 internalized upon treatment with PGD2 and 11-dehydro TXB2 in eosinophils of controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595 improved, whereas the DP antagonist MK0524 worsened inflammation in murine colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2 on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue, where it may contribute to inflammation, whereas DP most likely promotes anti-inflammatory actions. Copyright © 2014 by The American Association of Immunologists, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Animals -
- Antigens, CD3 - metabolism
- Blotting, Western -
- Colitis - chemically induced Colitis - metabolism
- Colitis, Ulcerative - metabolism
- Colon - drug effects Colon - metabolism Colon - pathology
- Dextran Sulfate -
- Female -
- Flow Cytometry -
- Humans -
- Immunohistochemistry -
- Indoles - pharmacology
- Killer Cells, Natural - metabolism
- Male -
- Mice -
- Mice, Inbred C57BL -
- Middle Aged -
- Neutrophils - metabolism
- Prostaglandin D2 - metabolism
- Receptors, Immunologic - antagonists & inhibitors Receptors, Immunologic - metabolism
- Receptors, Prostaglandin - antagonists & inhibitors Receptors, Prostaglandin - metabolism
- T-Lymphocytes - metabolism
- Th2 Cells - metabolism
- Young Adult -