Interferon-y Research Articles

Interferon-gamma mediates host resistance in a murine model of melioidosis.

Melioidosis is a life threatening infectious disease caused by the saprophytic gram-negative bacteria Burkholderia (formerly I?~eudomotias) pseirdomallei. In endemic areas particularly in South-east Asia and northern Australia, the bacteria can be isolated from many environmental sources especially soil, ponds and rice paddies [I]. Infection with Bpeudomallei occurs in both human and animals [ 1,2] with clinical presentation which range from prolonged latent asymptomatic infection to severely disseminated acute disease [3]. B.pseudomallei can cause infection in many different organ systems, however, from the histopathology studies of active melioidosis patients the pathological effect shows mainly in spleen, liver and lungs [4,5]. The ability of the bacteria to cause a long-term latent infection suggests that B.pseudomallei is capable of surviving intracellularly as has been demonstrated in vitro [6.7]. Nevertheless, the mechanisms of host resistance to infection with this increasingly important organism has not been clarified. In many other intracellular bacterial infections, interferon-y (IFN-y) has been shown to have an important role in the acute infection which has proved its capability to control or eradicate the infections [8,9]. In this study, we have estimated a mouse model of acute melioidosis and used this system to investigate the role of IFN-y in host resistance.

Aberrant activation of JAK/STAT pathway components in response to G-CSF, interferon-alpha/beta and interferon-gamma in NFS-60 cells.

There is evidence that the cellular responses to cytokines, such as granulocyte colony stimulating factor (G-CSF) and interferons, depend on prior activation of components of the JAK/STAT signalling pathway. We report here that the myeloid cell line NFS-60 shows aberrant JAK/STAT signalling yet elicits expected biological responses to G-CSF and interferons-alpha/beta and gamma. Instead of increased phosphorylation of JAK1 and JAK2 in response to G-CSF and interferon-gamma, and JAK1 and Tyk2 in response to interferon-alpha/beta, we observed only an increase of phosphorylation of Tyk2 in response to all of these cytokines in NFS-60 cells. The subset of STAT proteins being activated in response to these cytokines was unusual as well. G-CSF activated STAT3 and STAT5A, whereas interferons activated, in addition to STAT1 and STAT5 other, as yet unidentified, DNA binding proteins. However, NFS-60 cells show normal biological responses to these cytokines, such as proliferation in response to G-CSF, and reduction of proliferation, induction of an anti-viral response and induction of specific genes in response to interferons.

Protein myristoylation in human mononuclear phagocytes: modulation by interferon-y and tumor necrosis factor

Labelling of cells with [3H]myristic acid and analysis of labelled proteins by SDS-PAGE and fluorography, enabled the identification of a limited number of myristoylated proteins in human monocytes and monocyte-derived macrophages. In human monocytes, cultivated for one to three days, major myristoylated proteins observed were of 18 kDa, 44 kDa, 60-62 kDa, 90 kDa, and a doublet of 38-40 kDa. Differentiation of monocytes to macrophages by in vitro cultivation was accompanied by a selective decrease in the 60-62 kDa protein. Cultivation of the cells in the presence of the macrophage-activating cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), prevented the decrease in the expression of the 60-62 kDa myristoylated protein. The effect of cytokines was observed when monocytes were treated with IFN-gamma or TNF-alpha for 24 or 48 h and protein myristoylation analyzed at day four of culture. Maintenance of monocytes in culture for up to nine days in the presence of cytokines prevented the decrease in the expression of the 60-62 kDa myristoylated protein. IFN-gamma had additional effects on myristoylation of macrophage proteins. Treatment of monocytes with IFN-gamma for a few hours caused the induction of a 66 kDa protein. Induction of this myristoylated protein by IFN-gamma was time-dependent and peaked at six hours. Analysis of the subcellular distribution of the 66 kDa protein induced by IFN-gamma showed that, analogously to other myristoylated proteins, most of it was associated with cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

The inhibitory effects of prednisone, 16-methylen-prednisolone, and ACTH on con-A induced lymphokines (interferon-y) as measured by the chemiluminescence-activity of blood monocytes.

When lymphocytes are stimulated with mitogens or antigens they are enhanced via a cascade of lymphokines to produce interferon-y (IFN-y). IFN-y augments the H2O2 secretion of human monocytes which indirectly can be measured by chemiluminescence. We tested prednisone, 16-methylen-prednisolone and ACTH for their effect to inhibit the Con-A induced stimulation of the chemiluminescence-activity. All three hormones inhibited significantly the stimulation: prednisone up to 52.5% (concentration = 150 micrograms/ml, p = 0.000005), 16-methylen-prednisolone up to 22.5% (concentration = 2.5 micrograms/ml, p = 0.006) and ACTH up to 33% (concentration = 10 micrograms/ml, p = 0.0036).

Interferon-γ: pleiotropic effects on a rat pancreatic beta cell line

We have recently shown that interferon-y (IFN-y) markedly upregulates the expression of the class I major histocompatibility proteins on pancreatic beta cells and have therefore postulated that interferon-y may enhance cytotoxic lymphocyte-mediated beta cell damage in insulin-dependent diabetes mellitus. To further explore the interaction between interferon-γ and the pancreatic beta cell we have used the RIN-m5F insulinoma line to define the effects of interferon-γ on major histocompatibility protein expression, (pro)insulin and protein synthesis and cell growth. Interferon-γ induced a dose-dependent increase in the expression of the class I major histocompatibility proteins on the RIN-m5F cells, the maximal increase (10-fold) being seen at an interferon-γ concentration of 1 U/ml. The induction of class I proteins by interferon-γ was nearly completely abolished by cycloheximide. Expression of class II (la) proteins was not detected either in the presence or absence of interferon-y. (Pro)insulin and protein synthesis were decreased by 60% and 40%, respectively, in RIN-m5F cells cultured with interferon-γ (10 U/ml). Furthermore, the growth of RIN-m5F cells was significantly inhibited, and corresponding changes in cell morphology were evident, after 3 days of exposure to interferon-y (10 U/ml). These findings indicate that, in addition to its potential role in amplifying cytotoxic T cell activity against the pancreatic beta cell, IFN-y may also directly inhibit beta cell function and growth. Several mechanisms could therefore account for an ability of IFN-γ to compromise beta cell function and contribute to the pathogenesis of insulin-dependent diabetes.