Effects of differentiation/activation factors on the endotoxin-induced expression of MHC class II molecule and integrins, and production of cytokine by monocyte

Choi, Byong Son; Lee, Ho; Oh, Kwi Ok; Kim, Hyung Seop

Abstract

1,25-Dihydroxyvitamin D3(1,25(OH)2D3) and interferon-gamma(IFN-gamma) are capable of regulating cells in immune system and are representative differentiation inducer/activator of monocyte/macrophage lineage cells. They may affect the proinflammatory and immune effector functions of monocyte/macrophage activated with immunostimulants such as bacterial endotoxin. The expression of HLA-D, costimulatory adhesion molecules such as ICAM-1(CD54) and Mac-1(CD11b), and secretion of IL-1betawere used to evaluate the influence of 1,25(OH)2D3 and IFN-gammaon human promyelocytic cell line THP-1 cells. IFN-gammamarkedly induces the expression of ICAM-1 and HLA-D, and 1,25(OH)2D3 induces the expression of Mac-1 to a lesser extent. LPS alone markedly induces the expression of ICAM-1 molecule without any increase of HLA-D expression. LPS-induced ICAM-1 expression is synergistically increased by IFN-gammapriming, but fail to increase Mac-1 and HLA-D expression. IFN-gamma, 1,25(OH)2D3, and LPS separately do not induce the secretion of IL-1betaby THP-1, however, IL-1betasecretion is synergistically increased when THP-1 is exposed to the combination of IFN-gammaand LPS. LPS-induced IL-1betaproduction by IFN-gamma-primed cell is much higher when THP-1 have been previously exposed to 1,25(OH)2D3. In conclusion, these results show that expression of MHC class II and costimulatory adhesion molecules, and production of IL-1betaby cells of monocyte/macrophage lineage is highly regulated and monocyte /macrophage differentiation is required for optimal proinflammatory and immune reaction in response to exposure of bacterial endotoxin.