Two novel genes FIND and LIND differentially expressed in deactivated and Listeria-infected human macrophages

Abstract

Deactivation of macrophage functions plays an important role in human infectious and inflammatory diseases. In this study, differential-display RT-PCR was used to analyze the gene expression of human mononuclear phagocytes deactivated with interleukin (IL)-4, IL-10, and dexamethasone (DEX), in the absence and presence of infection with Listeria monocytogenes (Listeria). Two novel differentially expressed mRNA species were discovered: FIND (IL-Four INDuced) was upregulated with IL-4 but down-regulated with DEX, and is predicted to code for an M(r) 53,000 transmembrane protein. LIND (Listeria INDuced) was induced by Listeria infection, and is predicted to code for an M(r) 39,000 nuclear or cytoplasmic protein containing three coiled-coil domains. In addition, we report several novel effects of deactivators and infection on the expression of known genes: (1) IL-4 caused pronounced upregulation of ABCG2, coding for an ATP-binding cassette transporter highly expressed in the placenta, which mediates multidrug resistance of cancer cells, but is otherwise of unknown function; (2) both DEX and IL-4 downregulated osteopontin, an important factor of host resistance against intracellular infections; (3) inhibition of the CC-chemokine I-309 mRNA expression by all three deactivators in the presence of Listeria infection, and (4) upregulation by Listeria infection of the interferon-stimulated gene ISG20 of unknown function, whose product localizes with nuclear dots/PML bodies.