TY - JOUR
T1 - Recombinant IFN-α (2b) increases the expression of apoptosis receptor CD95 and chemokine receptors CCR1 and CCR3 in monocytoid cells
AU - Zella, Davide
AU - Barabitskaja, Oxana
AU - Casareto, Luca
AU - Romerio, Fabio
AU - Secchiero, Paola
AU - Reitz, Marvin S.
AU - Gallo, Robert C.
AU - Weichold, Frank F.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/9/15
Y1 - 1999/9/15
N2 - IFN-α-2b, known as potent immune modulator, can either inhibit or enhance immune cell activity within the tightly regulated microenvironment of inflammation, depending upon the concentration of the cytokine and the activation stage of the cell. Chemokine receptors, which not only mediate chemotaxis of immune cells to the site of inflammation but also affect cellular activation by transferring corresponding signals, represent yet another level of immune regulation. Here we demonstrate that IFN-α increases the expression of CCR1 and CCR3 in primary mononuclear phagocytes, as well as in the monocytoid cell line U937. Enhanced receptor mRNA expression correlated with functional readouts such as increased intracellular calcium mobilization and cell migration in response to ligands. Expression of CCR2b, CCR4, CCR5, and CXCR4 was unchanged or decreased after IFN-α treatment. These observations indicate a differentially regulated cellular signaling relationship of IFN-α pathways anal chemokine receptor expression. We also provide evidence that, under these conditions, IFN-α treatment increased the expression of CD95 (Fas, Apo1), resulting in enhanced susceptibility to apoptosis. Taken together, these data add important information for the rational application of IFN-α (2b) in immune and cancer therapies.
AB - IFN-α-2b, known as potent immune modulator, can either inhibit or enhance immune cell activity within the tightly regulated microenvironment of inflammation, depending upon the concentration of the cytokine and the activation stage of the cell. Chemokine receptors, which not only mediate chemotaxis of immune cells to the site of inflammation but also affect cellular activation by transferring corresponding signals, represent yet another level of immune regulation. Here we demonstrate that IFN-α increases the expression of CCR1 and CCR3 in primary mononuclear phagocytes, as well as in the monocytoid cell line U937. Enhanced receptor mRNA expression correlated with functional readouts such as increased intracellular calcium mobilization and cell migration in response to ligands. Expression of CCR2b, CCR4, CCR5, and CXCR4 was unchanged or decreased after IFN-α treatment. These observations indicate a differentially regulated cellular signaling relationship of IFN-α pathways anal chemokine receptor expression. We also provide evidence that, under these conditions, IFN-α treatment increased the expression of CD95 (Fas, Apo1), resulting in enhanced susceptibility to apoptosis. Taken together, these data add important information for the rational application of IFN-α (2b) in immune and cancer therapies.
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M3 - Article
C2 - 10477584
AN - SCOPUS:0033568286
SN - 0022-1767
VL - 163
SP - 3169
EP - 3175
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -