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Identifier

000459704

Title

Η ογκογόνος δράση της κυτοκίνης MIF : ανταγωνισμός MIF/HLA-DR για αλληλεπίδραση με την CD74 σε ένα κυτταρικό μοντέλο μυελογενούς λευχαιμίας

Alternative Title

Tumorigenic function of MIF cytokine: MIF/HLA-DR competition for interaction with CD74 in a myeloid leukemia cell line

Author

Μορφονιού, Θεολογία Π.

Thesis advisor

Αθανασάκη, Ειρήνη

Thesis advisor

Γκιζελή, Ηλέκτρα
Χαλεπάκης, Γεώργιος

Abstract

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine which is involved in many inflammatory diseases but also in cancer, as it influences cell proliferation, migration and angiogenesis. The biological activities of MIF depend on the interaction of MIF with its receptor, CD74. CD74 has a pivotal role in antigen presentation as an HLA class II chaperone molecule. Besides this role, CD74 is also a cell membrane high affinity receptor for MIF cytokine. The purpose of the present research study was the examination of MIF tumorigenicity and its competitive function against HLA class II molecules for CD74 binding. Therefore, focusing on the leukemic HL-60 cell line, HLA-DR-DP-DQ, CD74 and MIF membrane and intracellular expression but also the intracellular expression of HLA-DM and HLADO were examined. Furthermore, the effect of Interferon-γ on the expression of these molecules but also on the secretion of HLA-DR-DP-DQ, CD74 and MIF by HL-60 cells was studied. Finally, the intracellular distribution of the proteins of interest in the endocytic pathway was investigated. A possible MIF-CD74 interaction inside the endocytic pathway could intervene with the antigen presentation process as such an interaction would limit the availability of CD74 molecules for interaction with the HLA class II molecules, which may contribute to the impaired antigen presentation in acute myeloid leukemic cells.

Language

Greek

Subject

Class II histocompability molecules

Endocytic pathway

HL-60

Interferon-Gamma

Invariant chain (CD74)

Macrophage migration inhibitory factor (MIF)

Myeloid leukemia

Ενδοσωμικό μονοπάτι

Ιντερφερόνη-Γάμμα