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Prostaglandin E2 suppresses the expression and release of beta 2-microglobulin from mitogen-activated normal human
1Department of Medicine, Veterans General Hospital-Taipei, Taiwan, R.O.C.
Background:
Prostaglandin E2 (PGE2) is a feedback suppressor of immune response. Beta 2-Microglobulin (beta 2M) is part of HLA class I molecule that mediates viral antigen presentation to cytotoxic T lymphocytes as well as graft rejection. It has been known that beta 2M can be synthesized by both stimulated and unstimulated lymphocytes, but it is unknown whether beta 2M can be modulated by PGE2. This investigation aimed to clarify this point.
Methods:
Normal human mononuclear cells (MNC) were isolated, stimulated by phytohemagglutinin (PHA), and cultured for 3 days in the presence or absence of PGE2. The culture supernatants were collected and detected for beta 2M concentration by enzyme linked immunosorbent assays (ELISA). The cell pellets were stained indirectly with immunofluorescence for HLA-class I antigen and beta 2M expression on the surface membranes. In addition, the membrane potential of stimulated or unstimulated cells was measured by flow cytometry to evaluate the effect exerted by PGE2.
Results:
PGE2 at a concentration of more than 1 x 10(-8)M markedly suppressed the expression and release of beta 2M from PHA-stimulated MNC in a dose-dependent manner. Expression of HLA-class I molecule on PHA-stimulated MNC was also suppressed by PGE2. Kinetic study demonstrated that PGE2 began to suppress beta 2M synthesis of PHA-stimulated MNC from the 3rd day of culture. It also inhibited beta 2M release from lymphocytes in mixed lymphocyte reaction. This inhibitory effect was not due to cell death as confirmed by trypan blue exclusion. PGE2 per se exerts negligible effect on membrane potential of MNC but can normalize the depolarized state of the membrane induced by PHA as demonstrated by 3,3'-dihexyloxacarbocyanine iodide stain.
Conclusions:
PGE2 down-regulates the production of HLA-class I antigens and beta 2M molecules. This effect is associated with the suppression of cytotoxic T cell function by PGE2 and may be relevant to the underlying mechanism of PGE2 on this population of cells.