Interferon α selectively affects expression of the human myeloid cell nuclear differentiation antigen in late stage cells in the monocytic but not the granulocytic lineage

Abstract

The human myeloid cell nuclear differentiation antigen (MNDA) is expressed constitutively in cells of the myeloid lineage, appearing in myeloblast cells in some cases of acute myeloid leukemia and consistently being detected in promyelocyte stage cells as well as in all later stage cells including peripheral blood monocytes and granulocytes. The human myeloid leukemia cell lines, HL-60, U937, and THP-1, express similar levels of immunochemically detectable MNDA. Although, the level of MNDA mRNA in primary monocytes is very low it was up-regulated at 6 h following the addition of interferon alpha. The effect of interferon alpha on the MNDA mRNA is also observed in the cell lines HL-60, U937, and THP-1. The MNDA mRNA level in primary granulocytes was unaffected by addition of interferon alpha and other agents including interferon gamma, endotoxin, poly (I).poly (C), and FMLP. The MNDA mRNA level in the myeloid cell lines was also unaffected by the latter four agents. Induction of differentiation in the myeloid cell lines with phorbol ester induces monocyte differentiation which was accompanied by a decrease in MNDA mRNA level. This reduced level of mRNA could then be elevated with subsequent interferon alpha treatment. The effects of phorbol ester on MNDA mRNA appeared to be associated with induced differentiation since inhibiting cell proliferation did not alter the level of MNDA mRNA and cell cycle variation in MNDA mRNA levels were not observed. The ability of interferon alpha to up-regulate MNDA mRNA in phorbol ester treated myeloid cell lines is consistent with the observations made in primary monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Variable expression of human myeloid specific nuclear antigen MNDA in monocyte lineage cells in atherosclerosis

“…Interestingly, the level of MNDA mRNA in differentiated HL-60 cells or in cultured monocytes was upregulated with appropriate inducers [Briggs et al, 1994b], which is consistent with the observation that activated macrophages associated with inflammation can be induced to express a high level of MNDA. In the case of foam cells, the level of MNDA showed a delayed drop as foam cells developed in vitro [Shiffman et al, 2000].…”

The murine homolog of the HIN 200 family, Ifi 204, is constitutively expressed in myeloid cells and selectively induced in the monocyte/macrophage lineage

“…MNDA is expressed constitutively in cells of the myeloid lineage, appearing in promyelocyte stage cells as well as in all later stage cells including peripheral blood monocytes and granulocytes [20]. The level of MNDA mRNA in primary monocytes is very low and it is up-regulated at 6 h after the addition of IFN-␣ [15,18].…”

“…Expression of human MNDA gene is largely restricted to hemopoietic cells and associated with differentiation of cells of the myeloid and lymphoid lineage [20]. In the 5' flanking sequence of MNDA, several Myb and Ets binding elements are present, including an Ets-related PU.1 binding site known to be expressed specifically in M and B cells [28,34,35].…”

“…MNDA is specifically expressed in myeloid cells from the promyelocytic stage onward and is inducible only with IFN-␣. By contrast, IFI16 has been shown to be constitutively expressed in lymphoid cell lines, but is inducible with both IFN-␣ and -␥, and chemical agents in myeloid cells such as HL-60 [18][19][20][21]. This kind of tissue distribution, nuclear localization, and IFN-inducibility have suggested the designation of hemopoietic IFN-inducible nuclear proteins (HIN-200) [22].…”

The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations

“…We [25], IFI 16 is present in monocytes but not in granulocytes [12,26]. This restricted expression and the biochemical characteristics of IFI 16 and related proteins prompted us to examine the expression of IFI 16 in myeloid progenitor cells.…”