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J J Hooks

Publications and source records attributed to J J Hooks.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cytomegalovirus replication in human retinal pigment epithelial cells. Altered expression of viral early proteins.

PURPOSE: Cytomegalovirus (CMV) infections are frequent complications in patients who have undergone kidney and bone marrow transplant and in patients with acquired immune deficiency syndrome. The mechanism by which CMV is activated and replicated within the retina is unknown. The authors evaluated the ability of human CMV to initiate replication in human retinal pigment epithelial (RPE) cells and compared this system with CMV replication in human fibroblasts (HEL-299, MRC-5) and human amnion epithelial (WISH) cells. METHODS: Human RPE cells were obtained from donor eyes and propagated in vitro. Cells were infected, and CMV replication was evaluated in three ways: the detection of viral antigen by immunofluorescent, flow cytometry, and Western blot assays; the detection of virus-induced cytopathic effect (cpe), and the detection of infectious virus. RESULTS: No evidence of viral replication in the epithelial (WISH) cells was found. Although CMV does not usually replicate in vitro in epithelial cells, CMV replication was detected in RPE cells. There are a number of distinct differences in CMV replication in RPE cells compared to replication in human fibroblasts. Virus-induced cpe and the production of infectious virus by RPE cells were delayed when compared to virus infection in either HEL or MRC 5 cells. At a multiplicity of infection of 0.1 and 1, cpe and infectious virus yield reached maximum levels at days 4 to 5 in fibroblasts and at days 19 to 46 in RPE cells, respectively. Nevertheless, infectious virus produced by RPE cells (10(6.5) TCID50/0.1 ml) significantly surpassed levels produced by HEL cells (10(5.5)TCID50/0.1 ml). The permissive infection in RPE cells consisted of a prolonged period (5 to 6 days) of virus production in the absence of cytopathology. Virus protein expression evaluated by indirect immunofluorescence assays, Western blot analysis, and flow cytometry revealed a delay in viral protein expression in RPE cells compared to viral protein expression in fibroblasts. The pattern of viral protein evaluated by flow cytometry was noticeably different in the two cell types. At the middle phase of CMV replication in RPE cells, a low percentage of cells express immediate early (IE) protein at a time when a high percentage of the cells express early (E) proteins. This IE-1 protein is a stable protein found concurrently with E protein in fibroblasts. This difference in percentage of cells expressing specific CMV proteins is transient, that is, it does not remain apparent at 100% cpe. CONCLUSIONS: Retinal pigment epithelial cells appear to demonstrate a distinct pattern of CMV infection. The low frequency of expression of IE viral protein in RPE cells, the subsequent slow replication of CMV, and the altered expression of IE viral proteins may be critical variables that impact on their relationship to viral persistence and activation within the retina. Alterations in the IE gene product may indicate the existence of positive or negative nuclear transcription factors within infected RPE cells.

Blotting, Western↗
PubMed1995

Transforming growth factor-beta inhibits the cytokine-mediated expression of the inducible nitric oxide synthase mRNA in human retinal pigment epithelial cells.

Human retinal pigment epithelial (RPE) cells in culture respond to a mixture of cytokines (IFN-gamma, IL-1 beta, TNF-alpha) by producing large amounts of nitric oxide. Transforming growth factor-beta, unlike other growth factors, was found to inhibit this response by more than 75%. The expression of mRNA for the inducible form of nitric oxide synthase in RPE cells treated with cytokines was demonstrated by reverse transcription-polymerase chain reaction, sequencing of the PCR product and northern blotting. Transforming growth factor-beta was highly effective in inhibiting (by 75%) the cytokine-induced nitric oxide synthase mRNA expression. This response by RPE may play an important role in the etiology of infectious and inflammatory diseases affecting retina.

Base Sequence↗
PubMed1995

Bidirectional glutathione transport by cultured human retinal pigment epithelial cells.

PURPOSE: To characterize glutathione (GSH) transport by cultured human retinal pigment epithelial (HRPE) cells. METHODS: Cultured HRPE cells were pretreated with acivicin for GSH efflux and with buthionine sulfoximine for GSH uptake to prevent the breakdown and resynthesis of GSH. Efflux was measured by the linear rate of accumulation of GSH in the supernatant; uptake was measured using [35S] GSH plus varying concentrations of GSH. Molecular forms were verified by high-performance liquid chromatography. HRPE cell mRNA was probed for the presence of the two recently cloned rat sinusoidal and canalicular GSH transporters, (RsGshT and RcGshT), by Northern blot analysis. RESULTS: Glutathione efflux was temperature dependent (undetectable at 4 degrees C), and its averaged 23 +/- 3.3 pmol/10(6) cells/minute or 10% of the total GSH effluxed per hour (total cell GSH = 13.6 +/- 1.5 nmol/10(6) cells). Efflux was not influenced by dithiothreitol or sulfobromophthalein-reduced GSH adduct, agents known to affect liver sinusoidal GSH transport. Glutathione uptake was linear up to 45 minutes and was temperature dependent. The difference between 37 degrees C and 4 degrees C uptake values represented true uptake. Glutathione uptake (2 microCi/ml + 1 mM mass) was Na independent and was inhibited significantly by phenol-3,6-dibromphthalein disulfonate. The kinetics of GSH uptake was assessed by measuring uptake with 35S-GSH and 0.05 to 40 mM extracellular GSH for 30 minutes. Uptake was saturable with Vmax = 18.7 +/- 1.7 nmol/10(6) cells/30 minutes, Km = 12.1 +/- 1.9 mM, n (binding site) = 1. On Northern blot analysis, HRPE cells express mRNA for RcGshT but not for RsGshT. CONCLUSIONS: The similarities in functional characteristics of GSH transport and the presence of RcGshT-like mRNA suggest GSH transport in HRPE cells is mediated by a RcGshT homolog. Although the transporter can operate bidirectionally, it is expected to be a net efflux pump under normal physiologic conditions because the intracellular GSH concentration is much higher.

Biological Transport↗
PubMed1994

Increased expression of heme oxygenase-1 in human retinal pigment epithelial cells by transforming growth factor-beta.

Antibodies specific for heme oxygenase-1 (HO-1) were produced in rabbits, using the multiple antigen peptide (MAP) technique, and were employed to investigate the ability of transforming growth factor-beta 1 (TGF-beta 1) to induce the HO-1 protein in cultured human retinal pigment epithelial (RPE) cells. Western blot analyses showed that the cytokine induced HO-1 in these cells in a time- and dose-dependent manner. TGF-beta 1 also increased the mRNA for HO-1 in treated cells prior to the increase in HO-1 protein. The induction was effectively blocked by a neutralizing antibody preparation against TGF-beta 1. When tested under similar conditions, other growth factors such as basic fibroblast growth factor-I, platelet-derived growth factor, insulin-like growth factor, transforming growth factor-alpha, and epidermal growth factor did not show appreciable induction of HO-1. Lipopolysaccharide, tumor necrosis factor-alpha, and interferon-gamma were also not inducers, although TGF-beta 2 effectively induced HO-1. Heavy metal ions and thiol reagents were also highly potent inducers of HO-1 in human RPE cells. The induction of HO-1 by TGF-beta 1 was also observed in bovine choroid fibroblasts, but not in HELA, HEL or bovine corneal fibroblasts. Our results demonstrate for the first time that HO-1 can be induced by an important cytokine, TGF-beta 1, causing an increase in the expression of both HO-1 message and protein in specific neuroepithelial and fibroblast cells.

Amino Acid Sequence↗
PubMed1994

Synergistic effects of gamma interferon on inflammatory mediators that induce interleukin-6 gene expression and secretion by human retinal pigment epithelial cells.

The retinal pigment epithelial (RPE) cell is a potent regulatory cell within the retina. It helps to maintain normal retinal activity, and following gamma interferon (IFN-gamma) exposure, it may express major histocompatibility complex class II molecules and function as an antigen-presenting cell. Since interleukin-1 (IL-1) and IL-6 are potent cytokines observed in ocular inflammatory processes, we initiated studies to evaluate conditions which enable RPE cells to produce these cytokines. Cultures of human RPE cells from two eye donors were established and characterized, and enzyme immunoassays were employed to screen for IL-1 and IL-6 production. Treatment of RPE cells with lipopolysaccharide (LPS) or recombinant tumor necrosis factor alpha, IL-1, or IFN-gamma resulted in a significant level of secretion of IL-6. In contrast, treatment with recombinant epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, or transforming growth factor alpha, or LPS can dramatically augment the secretion of IL-6 by RPE cells. Thus, these inflammatory mediators can act alone or synergistically with IFN-gamma to activate RPE cells and dramatically increase the expression and secretion of IL-6. In contrast, IL-1 was not detected following stimulation with any of the above-mentioned cytokines or LPS. Characterization of IL-6 protein production by RPE cells revealed that 98% of the protein is promptly secreted by the cell, its induction is dependent upon the time and concentration of the stimulant, and the continuous presence of the stimulant is required for IL-6 production. Moreover, Western blot (immunoblot) analysis of secreted proteins revealed that IL-6 was produced in multiple molecular forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

Retina and retinal pigment epithelial cell autoantibodies are produced during murine coronavirus retinopathy.

The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. In the early phase of the disease, day 1 to 7, a retinal vasculitis is noted and is associated with the presence of virus particles. In the late phase of the disease, day 10 to 140, a retinal degeneration is observed and is associated with the absence of both virus particles and inflammatory cells. We show that the retinal degenerative process is also associated with the presence of antiretinal autoantibodies. In total, 22 of 23 sera collected from 10 to 70 days after JHM virus inoculation contained antiretinal autoantibodies. These autoantibodies are not found in sera from normal or mock-injected mice. Antibodies to retinal tissue were identified as two distinct patterns of immunoperoxidase staining on frozen sections of normal rat eyes, retinal autoantibodies and retinal pigment epithelium (RPE) autoantibodies. The antiretinal autoantibodies first appeared as IgM class antibodies that shifted to IgG class autoantibodies. The anti-RPE cell autoantibodies were predominantly of the IgG class. Sera that were positive for these autoantibodies did not stain with liver or kidney sections but 2 of 3 did react with rat brain sections. A second mouse strain, CD-1, was also evaluated because these animals respond to JHM virus inoculation by developing only the early phase of this disease, i.e. vasculitis. On day 10 postinoculation, the retina architecture has a normal appearance. In these mice, which are free of a retinal degeneration, antiretinal autoantibodies are not produced. However, just as is noted in the BALB/c mice, antivirus neutralizing antibodies are produced in the infected CD-1 mice. These findings suggest a role for autoimmunity in the pathogenesis of murine coronavirus induced retinal degeneration. This study establishes an animal model for the study of humoral autoimmune responses in human retinal degenerations.

Animals↗
PubMed1993

Molecular cloning and expression of RPE65, a novel retinal pigment epithelium-specific microsomal protein that is post-transcriptionally regulated in vitro.

Studies reported previously from this laboratory have shown that microsomal membranes of the vertebrate retinal pigment epithelium (RPE) contain an RPE-specific 65-kDa protein, RPE65, which bears the determinant recognized by the strictly tissue-specific monoclonal antibody RPE9, and which is developmentally regulated (Hamel, C. P., Tsilou, E., Harris, E., Pfeffer, B. A., Hooks, J. J., Detrick, B., and Redmond, T. M. (1993) J. Neurosci. Res. 34, 414-425). Microsequencing of 17 tryptic and chymotryptic peptides obtained from the in situ digestion of the RPE65 blotted on nitrocellulose yielded primary sequences that were used to generate oligonucleotide probes. An 84-nucleotide guessmer was used to isolate two clones from a bovine RPE lambda Zap II cDNA library. Rapid amplification of cDNA ends was used to complete the 5' and 3' ends, resulting in a 3,115-base pair composite cDNA. The open reading frame encodes a novel protein of 533 amino acid residues with a computed molecular weight of 60,940. This protein does not match any other sequence in the data bases. The 231 amino acids obtained from peptide sequencing match 43% of the amino acid sequence deduced from the cDNA. The protein has a calculated pI of 6.41 and is not predicted to have any transmembrane segments. The open reading frame expressed in Escherichia coli has an apparent molecular weight identical to that of the native protein and is recognized by the monoclonal antibody RPE9, further corroborating its validity. Northern blot analysis detected a major mRNA species of 3.15 kilobases for RPE65, as well as shorter species, only in RPE and not in other tissues (including other ocular tissues). Cultured RPE cells (7 weeks in primary culture) contained RPE65 mRNA in amounts equivalent to fresh RPE. Such cells, however, contained no immunodetectable RPE65. The possible structure of this RPE-specific protein and hypotheses for the absence of translation in vitro are discussed.

Amino Acid Sequence↗
PubMed1993

A developmentally regulated microsomal protein specific for the pigment epithelium of the vertebrate retina.

In the vertebrate retina, the retinal pigment epithelium (RPE) performs specific functions critical to the normal process of vision. Although some of these functions are well documented, molecular data are still scarce. Using the RPE-specific monoclonal antibody RPE9, raised against human RPE cells, we have identified a novel 65 kD protein, conserved in mammals, birds, and frogs. This RPE-specific protein was found to be nonglycosylated. It was most effectively solubilized in the presence of detergent suggesting that it is associated with the RPE cell membranes. Its partitioning in the detergent phase of Triton X-114 and its solubilization in 0.75 M and 1.0 M KCl suggest that it interacts with the membrane either through a polypeptide anchor or charged amino acids. Cell fractionation by differential solubilization and differential centrifugation demonstrated that the protein was preferentially associated with the microsomal membrane fraction, where it is the major protein. Developmental expression of this 65 kD protein was examined in neonatal rats. Morphologically well-differentiated RPE cells did not express the 65 kD protein at birth. However, expression was detectable at postnatal day 4, that is, one to two days before the photoreceptors develop their outer segments, suggesting that the expression of the 65 kD protein may be coordinated with other developmental events in the intact retina. This is further supported by the fact that RPE cells in confluent culture lose the expression of this protein within two weeks, while they maintain their characteristic epithelial morphology. Because of its specificity, its evolutionary conservation, and its timing of expression, it is possible that this protein may be involved in one of the key roles of RPE and as such is an important molecular marker for RPE differentiation.

Animals↗
PubMed1993

Coronavirus (JHM) replication within the retina: analysis of cell tropism in mouse retinal cell cultures.

The murine coronavirus, mouse hepatitis virus, JHM strain, induces a retinal degenerative disease in adult BALB/c mice. Coronavirus infections are highly species specific with virus exhibiting a strong tissue and cell specificity. In this report we evaluated the cellular basis of JHM virus retinal tropism. Retinal cultures and retinal pigment epithelial (RPE)-retinal mixed cell cultures were prepared from eyes obtained from Balb/c mice. The ability of JHM virus to infect and replicate in these retinal cultures was evaluated by light microscopy, immunofluorescent staining, electron microscopy, and virus isolation. Cytopathology was not observed and virus could not be detected in supernatant fluid in retinal cultures. However, low levels of infectious virus could be detected within the cells for the first 4 days. This observation suggested that cell-to-cell interactions may be critical since virus particles and virus antigens can be seen in vivo within the neural retina and the RPE. In contrast to the retinal cultures, retinal-RPE mixed cultures were supportive to JHM virus replication. Syncytial cytopathology was observed for the first 4 days and virus was isolated from supernatant fluids. By electron microscopy, virus was found intracellularly within vacuoles and extracellularly at the plasma membrane. After Day 4, a persistent virus infection was established in which cells produced virus for 5 weeks without cytopathic effects or cell death. Double-labeling immunofluorescent studies of retinal-RPE mixed cultures showed that the virus antigen was co-expressed with a Muller cell marker, glutamine synthetase. This cell is the most prominent glial element in the retina. These studies demonstrate that JHM virus is capable of establishing a persistent virus infection in mixed retinal (Muller)-RPE cell cultures. Moreover, these data suggest that cell-to-cell interactions influence the establishment of coronavirus infections in the retina.

Animals↗
PubMed1993

Ultrastructural localization of RPE-associated epitopes recognized by monoclonal antibodies in human RPE and their induction in human fibroblasts by vitreous.

Electron microscopic immunocytochemistry was performed to localize the epitopes recognized by monoclonal antibodies RPE15 and RPE9, reported to specifically stain retinal pigment epithelial (RPE) cells by light microscopy, and to evaluate the usefulness of these antibodies for recognizing phenotypically altered, pathological RPE cells. The labeling patterns of the two antibodies were indistinguishable, and in human eyes positivity was limited to RPE cells. In in situ and vitreous-cultured human RPE cells the epitopes were localized to the surface and intracellular membranes and to the cytoplasm. In vitreous culture many RPE cells developed processes containing filaments which reacted with either antibody. Human retinal glial cells were negative. Some human fibroblasts in vitreous culture showed labeling of the same structures as RPE cells with either antibody, limiting the usefulness of these antibodies for distinguishing RPE cells from fibroblasts, which can assume similar morphologies when in contact with vitreous; however, they may be useful adjuncts to anti-cytokeratin antibodies for RPE cell identification in various pathological conditions.

Cells, Cultured↗
PubMed1993

Modulation of major histocompatibility complex class 1 genes in human retinoblastoma cells by interferons.

PURPOSE: To examine the mechanism(s) of interferon (IFN) induced expression of major histocompatibility complex (MHC) class 1 molecules on the human retinoblastoma cell line, Y-79. METHODS: Y-79 cells were incubated in the presence of IFN-alpha, -beta, and -gamma. Y-79 cell expression of MHC class 1 molecules was measured by flow cytometric analysis. HLA-B7 and oncogene transcription were evaluated by Northern blot analysis and nuclear runoff transcription assays. RESULTS: IFN-gamma increased MHC-class 1 antigen expression and induced a fivefold increase in its transcription rate. Posttranscriptionally, IFN-beta and -gamma increased steady state messenger RNA for the HLA-B7 gene. These effects were not associated with down regulation of N-myc oncogene nuclear transcription. Moreover, dexamethasone did not affect the IFN-gamma induced expression of MHC-class 1 molecules. CONCLUSIONS: Both transcriptional and posttranscriptional mechanisms are implicated in the modulation of class 1 molecule expression by IFN. In addition, this modulation is not associated with down regulation of N-myc oncogene expression. Spontaneous or IFN-gamma induced MHC class 1 antigen expression in retinoblastoma Y-79 cells is resistant to glucocorticoid hormones.

Blotting, Northern↗
PubMed1992

Redistribution and reduction of interphotoreceptor retinoid-binding protein during ocular coronavirus infection.

Inoculation of the neurotropic coronavirus mouse hepatitis virus strain JHM intravitreally or into the anterior chamber causes acute infection of the retinal pigment epithelium (RPE) and neural retina. Weeks later, many retinas have foci of moderate to severe atrophy. The effect of coronavirus infection (after intravitreal inoculation) was examined on interphotoreceptor retinoid-binding protein (IRBP), the glycolipoprotein in the interphotoreceptor matrix (IPM) thought to transport retinoids between the photoreceptors and the RPE. Changes in IRBP distribution accompanied virus-associated retinal pathology, including photoreceptor loss and RPE abnormalities. Immunohistochemistry on days 3 and 6 showed that IRBP had diffused into the neural retina away from the IPM. The IRBP became localized abnormally in the same areas as virus-induced lesions, shown by staining adjacent sections with a monoclonal antibody specific for the viral nucleocapsid protein. Moreover, the level of IRBP in isolated retinas, measured in an immunoslot-blot assay, decreased significantly by day 3 and remained low through day 23. This decrease was confirmed in eyecups isolated on day 6. It may be caused in part by loss of photoreceptors and diffusion of IRBP through the retina into the vitreous. These studies show that a virus may induce an acute, limited infection in the retina that can be cleared by the host. However, the infection initiated a series of events resulting in long-term reduction and redistribution of a critical photoreceptor protein.

Animals↗
PubMed1991

Leukoregulin, a novel cytokine enhances the anti-herpesvirus actions of acyclovir.

Leukoregulin is a naturally occurring immunologic cytokine which increases membrane permeability and drug uptake in tumor cells but not in normal cells. In this paper we show that leukoregulin also increases membrane permeability of Herpes simplex virus type 1 (HSV-1)-infected cells. More importantly, we demonstrate that leukoregulin significantly enhances the ability of acyclovir (acycloguanosine, ACV) to inhibit the cellular release of infectious HSV-1. The ability of 1-100 microM ACV to inhibit infectious HSV-1 production is increased up to 100-fold when HSV-1-infected human amnion (WISH) cells are treated with 5 units leukoregulin/ml and ACV 3 hr after virus infection. Under these conditions, leukoregulin alone is unable to inhibit HSV-1 infectivity. In addition, three unrelated cytokines, interleukin-1 alpha (IL-1), interferon (IFN)-alpha and IFN-gamma lack the ability to enhance the anti-HSV actions of ACV when their treatment is initiated after HSV-1 infection. These findings demonstrate that a combination of immunotherapy and chemotherapy can produce a substantial inhibition of herpesvirus replication and provide a rationale for the application of this approach to the interventive treatment of virus infection.

Acyclovir↗
PubMed1991

1990 Sir Henry Wellcome medal and prize winner. Leukoregulin: a new biotherapeutic cytokine in the search for more effective anti-viral pharmacologic agents.

This investigation examines whether cytokines, as exemplified by leukoregulin, with their immense potential for biorecognition and target cell modulation as a result of their complex three-dimensional structure, have the potential to provide new directions for biotherapy of infectious disease. Leukoregulin is a naturally occurring immunologic cytokine, secreted by stimulated lymphocytes, which increases membrane permeability and drug uptake in tumor but not in normal cells. This study demonstrates that leukoregulin also increases the plasma membrane permeability of cells acutely infected with herpes simplex type 1 virus and that the increase in membrane permeability is accompanied by a 10- to 100-fold increase in the ability of acyclovir to inhibit the release of infectious virus when the cells are treated with leukoregulin 3 hours after infection with the virus. This is the first demonstration that a cytokine, alone or in combination with anti-viral chemotherapy, can effectively inhibit virus replication in human cells following acute virus infection, which indicates that combination immunotherapy and chemotherapy have the potential to completely inhibit the production of infectious virus by acutely infected human cells.

Acyclovir↗
PubMed1991

Ocular tropisms of murine coronavirus (strain JHM) after inoculation by various routes.

The coronavirus mouse hepatitis virus (MHV, strain JHM) infects tissues in the anterior and posterior segments when injected intravitreally into adult mouse eyes. Infection causes progressive damage to the photoreceptors and retinal pigment epithelium (RPE), resulting in a disease the authors have termed JHM retinopathy. To determine whether this virus is retinotropic independent of route of inoculation, the authors injected mice with virus by several different routes: into the anterior chamber (AC), onto the cornea, intranasally, or intracerebrally. Inoculation into the AC produced effects similar to those after intravitreal inoculation, although slightly slower in onset. Viral antigen was detected in the anterior portion of the iris on day 3, and by day 6, was also located primarily in the inner nuclear layer, photoreceptors, Müller cells, and RPE. However, by day 10, viral antigens were only detected in a few cells in the ganglion cell layer. Infectious virus was isolated from neural retinas on days 3 and 6, but not on day 10. In contrast, infectious virus could not be isolated from contralateral eyes. After 14 weeks, specific regions of some retinas were atrophied, with most of the retinal layers involved. Inoculation by other routes also resulted in virus-induced disease. Scarification of the cornea with virus, but not application of virus droplets alone, caused pathologic changes in the corneal epithelium and stroma and subtle effects on the ganglion cell and inner plexiform layers. Intracerebral inoculation of virus affected mainly the RPE. Pathologic effects and viral antigens were not detected in eyes from four mice inoculated intranasally. These results show that a murine coronavirus is retinotropic when introduced by several direct routes and one indirect route. Moreover, these studies show that long-lasting retinal disorders ranging in intensity from mild to severe can occur after coronavirus infection.

Animals↗
PubMed1991

Cytokine-induced modulation of cellular proteins in retinoblastoma. Analysis by flow cytometry.

Cytokines are a group of specialized, hormone-like proteins that can exert profound influences on cellular development and on a variety of cellular functions. Retinoblastoma cells are an important model for exploring human malignancy and differentiation. These multipotent embryonic cells are capable of differentiating into neuronal, glial-like and retinal pigment epithelium (RPE)-like elements. This report shows that flow cytometric analysis can be used to measure the expression of both cytoplasmic and cell surface proteins in retinoblastoma cells. The authors used this technique to monitor changes in the expression of selected cellular proteins after exposure to specific cytokines and found that MHC class I molecules were augmented by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), but not by tumor necrosis factor (TNF). However, the MHC class II molecules were augmented by IFN-gamma but not by IFN-alpha or TNF. The neuronal markers, IRBP and PR-6, the glial-like marker, GFAP, and the RPE cell markers, RPE-9 and RPE-15, were not altered by any of the cytokines tested. Furthermore, IFN-gamma induced a striking enhancement of the expression of the photoreceptor cell protein, S-antigen. In contrast, IFN-alpha and TNF did not affect the expression of S-antigen. These studies show that the cytokine, IFN-gamma, can enhance a distinct cellular protein associated with cells committed to a specific cell lineage.

Antigens↗