|
|
| Identifier |
000366903 |
| Title |
Η αλληλεπίδραση λεμφοκυττάρων και κολονικών επιθηλιακών κυττάρων στη φλεγμονώδη εντεροπάθεια, ο ρόλος των χημειοκινών |
| Alternative Title |
Crosstalk between epithelial cells and T lymphocytes in inflammatory bowel diseases the role of chemokines. |
|
Author
|
Μανούσου, Πηνελόπη
|
|
Thesis advisor
|
Κόλιος, Γεώργιος
|
|
Reviewer
|
Παπαδάκης, Κων/νος
Κουτρουμπάκης, Ιωάννης
Κουρούμαλης, Ηλίας
Μουζάς ,Ιωάννης
Παπαδάκη,Ελένη
Θερμού, Κυριακή
|
| Abstract |
Ηuman colonic epithelial cells express Thl-associated chemoattractants, yet little is known about the production of Th2-associated chemoattractants. Furthermore, T-lymphocyte migration is implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). CXC chemokines MIG, IP-10, and I-TAC act by binding to the CXCR3A or the splice variant CXCR3B receptor on Thl-lymphocytes. On the other hand, CC chemokines, CCL11/Eotaxin-1, CCL24/Eotaxin-2, and CCL26/Eotaxin-3 are known to attract CCR3-expressing, Th2-polarized lymphocytes. We investigated the role of these CXC and CC chemokines and their receptors in patients with UC, CD, and normal controls (NC).
Methods We studied constitutive and inflammation-induced expression and production of CXCR3 and CCR3 together with their ligands in the colon and CD3+ peripheral blood lymphocytes of patients with inflammatory bowel diseases (IBD) by flow cytometry, reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). We further defined the regulated expression of these chemokines by RT-PCR and ELISA using cultured human epithelial cell lines. Thus, HT-29 and Caco-2 colonic epithelial cells were studied following in vitro stimulation with pro-inflammatory (Th1) and Th2-derived cytokines.
Results
CXCR3A mRNA (full size) expression was found in CD3+ PBL from normal controls and UC patients, but not from CD patients. In contrast, CD3+ PBL from CD patients showed a marked mRNA expression of the spliced variant CXCR3B. This finding could explain the high expression of CXCR3 on CD3+ PBL from CD patients in flow cytometry. Increased chemokines expression and production was found in colonic biopsies and serum from CD compared to UC patients and normal controls. Stimulation of epithelial cells with Th1 proinflammatory cytokines significantly induced chemokines production. The addition of Th2-derived cytokines had an inhibitory effect. Stimulation of Jurkat cells with cytokines and supernatant conditioned media from epithelial cells induced CXCR3A or CXCR3B expression depending on the stimuli.
When CC chemokines were examined, a higher fraction of peripheral T lymphocytes were found to be positive for CCR3 in patients with ulcerative colitis (UC) compared to Crohn's Disease (CD) whilst almost no CCR3+ T cells were found in normal controls (NC). Similarly, higher and more frequent expression of CCR3 was observed in colonic biopsies from patients with UC-regardless of the disease activity-when compared to CD or NCs. Serum CCL11/Eotaxin-1 was significantly increased in UC (306±87pg/ml) and less so in CD (257±43pg/ml) whereas CCL24/Eotaxin-2, and CCL26/Eotaxin-3 were increased only in UC. Colonic expression of the three chemokines was minimal in NCs but high in IBD (especially UC) and was independent of disease activity. Th2 and to a lesser extent Th1 cytokines were able to induce expression and production of all three eotaxins from colonic epithelial cells in culture.
Conclusions
These data demonstrate that PBL from CD patients express a spliced variant of the CXCR3 receptor and suggests that epithelium can play a role in modulating pathologic T cell-mediated mucosal inflammation.
Furthermore CCR3 and ligands over-expression would appear to be a characteristic of UC. The production of CCR3 ligands by human colonic epithelial cells further supports the important role of epithelium - lymphocyte interaction in the pathogenesis of IBD
|
| Language |
Greek |
| Subject |
Chemokines |
|
Colonic epithelial cells |
|
Gastrointestinal system |
|
Inflammatory bowel doseases |
|
T Lymphocytes |
|
Γαστρεντερικός σωλήνας |
|
Ιδιοπαθείς φλεγμονώδεις εντεροπάθειες |
|
Κολονικά επιθηλιακά κύτταρα |
|
Τ λεμφοκύτταρα |
|
Χημειοκίνες |
| Issue date |
2010-07-20 |
| Collection
|
School/Department--School of Medicine--Department of Medicine--Doctoral theses
|
|
|
Type of Work--Doctoral theses
|
| Views |
247 |
Η αλληλεπίδραση λεμφοκυττάρων και κολονικών επιθηλιακών κυττάρων στη φλεγμονώδη εντεροπάθεια, ο ρόλος των χημειοκινών
