Hepatitis C-associated peripheral corneal ulceration: rapid response to intravenous steroids.

Purpose: We present a case of peripheral corneal ulceration in a patient with hepatitis C, which rapidly and dramatically responded to intravenous steroid treatment.

Methods: Clinical examination and photographs were obtained to document initial presentation and therapeutic response of Mooren's-type ulcers to steroids.

Results: Bilateral peripheral corneal ulceration with documented progression responded to intravenous administration of steroids within 5 days.

Gelatinase B and A expression after laser in situ keratomileusis and photorefractive keratectomy.

Objective: To compare the expression of gelatinases in the corneal epithelium and stroma after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK).

Methods: Rabbit eyes were treated with LASIK (n=11), PRK (n=12), or corneal flap construction (n=12); 4 eyes served as unwounded controls. Zymography was performed on the central epithelium and the stroma 1, 3, and 7 days after surgery to determine the expression of gelatinases.

Colchicine down-regulates lipopolysaccharide-induced granulocyte-macrophage colony-stimulating factor production in murine macrophages.

Activation of macrophages by LPS and taxol results in production of IL-1, IL-6, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF), which are involved in regulating hemopoiesis, inflammation, and immune responses. Microtubules are proposed as a target site for LPS interaction(s), based on similarities between the effects of the tubulin-binding drug taxol and LPS. To clarify the role of microtubules in LPS-induced GM-CSF expression in macrophages, we examined whether microtubule depolymerizing agents affect GM-CSF production in macrophages.

IL-6 induction of protein-DNA complexes via a novel regulatory region of the inducible nitric oxide synthase gene promoter: role of octamer binding proteins.

Macrophage inducible nitric oxide synthase (iNOS) catalyzes the synthesis of NO. IL-6-stimulated macrophage differentiation of murine myeloid M1 cells is accompanied by iNOS gene induction and steady-state mRNA expression. Two regions within the iNOS promoter mediate transcriptional responsiveness to LPS and IFN-gamma.

Expression of human glucocerebrosidase in murine macrophages: identification of efficient retroviral vectors.

Gaucher's disease is an autosomal recessive disorder characterized by a functional deficiency in beta-glucocerebrosidase enzymatic activity and the resultant accumulation of the glycolipid glucocerebroside in macrophages. Due to the nature of the affected cells, Gaucher's disease is an excellent candidate for gene therapy of hematopoietic stem cells and autologous bone marrow transplantation of transduced cells using retroviral vectors containing the glucocerebrosidase (GC) gene. In order to identify a retroviral vector capable of high levels of expression of the GC gene in macrophages, we have used the murine myeloid leukemia cell line, M1, a cell line that can be differentiated with interleukin-6 (IL-6) from blasts to macrophages.

Taxol induces the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor in murine B-cells by stabilization of granulocyte-macrophage colony-stimulating factor nuclear RNA.

Taxol, a microtubule-stabilizing agent, has been shown to have antineoplastic activity against various tumors. In addition, it has been shown that taxol resembles bacterial lipopolysaccharide in its ability to activate macrophages. Recently we have shown that lipopolysaccharide induces the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) in murine B-cell lines.

Facilitation of cocaine kindling by glucocorticoids in rats.

We report that glucocorticoids significantly facilitated the development of cocaine-induced kindled seizures. These results suggest that glucocorticoids may have effects on the development of kindled seizures which are similar to those of the neuropeptide, corticotropin-releasing hormone (CRH), with which they show a close functional relationship. These results may be of interest in the light of data showing that glucocorticoids increase CRH expression in the central nucleus of the amygdala, which is an important site for the development of kindling.

Interferon-gamma antagonizes interleukin-6-induced expression of interleukin-4 receptors in murine myeloid cells by a transcriptional mechanism.

The murine myeloid leukemia cell line M1 induced by interleukin-6 (IL-6) is a model system to study the differentiation of blast cells to mature macrophages. We have recently shown that IL-6 induces the expression of the IL-4 receptor (IL-4R) in these cells. In the present study we investigate the mechanism of action of interferon-gamma (IFN-gamma), an antagonist of IL-4 in numerous cells and a cofactor in both induction and suppression of myelopoiesis, on the expression of IL-4R.

Interferon-gamma destabilizes interleukin-1-induced granulocyte-macrophage colony-stimulating factor mRNA in murine vascular endothelial cells.

Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines:interleukin-1 (IL-1), which induces the production of GM-CSF, and interferon gamma (IFN-gamma), which downregulates this production. The GM-CSF gene is constitutively transcribed in these cells and the transcription rate of the GM-CSF gene does not change with either IL-1 alone or IL-1 plus IFN-gamma.

Evaluation of expression of transferred genes in differentiating myeloid cells: expression of human glucocerebrosidase in murine macrophages.

The retroviral vector LGSN, in which the human glucocerebrosidase (GC) cDNA is driven by the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR), was tested for expression in the murine myelomonocytic leukemia cell line M1 before and after induction of differentiation with interleukin-6 (IL-6). Southern analysis of the seven transduced clones selected for neomycin resistance in Geneticin (G-418 sulfate) demonstrated one to eight copies of intact provirus with rearrangements in only two clones. Absolute levels of human GC RNA and protein increased with increased copy numbers of provirus in the clones.

Ca2+ ionophore A23187-dependent stabilization of granulocyte-macrophage colony-stimulating factor messenger RNA in murine thymoma EL-4 cells is mediated through two distinct regions in the 3'-untranslated region.

We analyze the role of the Ca2+ ionophore A23187 in the induction of GM-CSF mRNA expression in EL-4 thymoma cells. Northern analysis shows that A23187 increases the half-life of GM-CSF mRNA. To identify potential Ca2+ response elements in the GM-CSF mRNA, we produced stable transfectants containing pRSV-CAT (EL-4cat) or hybrid constructs in which most of the GM-CSF 3'-untranslated region (EL-4gm) or the adenosine-uridine boxes alone (EL-4au) were placed in a downstream position from the CAT coding region.

Dissociation of early and late markers of murine myeloid differentiation by interferon-gamma and interleukin-6.

Murine myeloid leukemia M1 cells undergo terminal differentiation to mature macrophages after stimulation with interleukin-6 (IL-6). This process can be monitored by measuring the expression of early markers such as the high affinity receptor for monomeric IgG2a (Fc gamma RI) and Ia antigen followed by late markers such as lysozyme production and finally morphological changes from blast cells to mature macrophages. The same early markers that are expressed on M1 cells after induction with IL-6 are also expressed on monocytic cells after activation with interferon-gamma (IFN gamma).

Soluble interleukin-4 receptor production by murine myeloid progenitor cells: induction by interleukin-6 and interferon-gamma.

Soluble cytokine receptors, molecules that can selectively modulate the effects of a single cytokine, have generated great interest both as indicators of disease and as targeted immunotherapeutic agents. However, cellular sources for soluble cytokine receptors are not well characterized and the regulation of soluble receptor production is not clear. We recently found that interleukin 6 (IL-6) induces the expression of membrane-bound interleukin 4 (IL-4) receptors (mIL-4R) in the murine myeloid leukemia M1 cell line.

Binding of sequence-specific proteins to the adenosine- plus uridine-rich sequences of the murine granulocyte/macrophage colony-stimulating factor mRNA.

Adenosine+uridine (AU)-rich sequences in the 3' untranslated region (3'UTR) of the mRNA of many cytokines and oncogenes play an important role in mediating RNA degradation. Among the cytokines containing such AU-rich sequences in their 3'UTR is the hematopoietic growth factor granulocyte/macrophage colony-stimulating factor (GM-CSF). GM-CSF gene expression in T cells is regulated by modulation of mRNA half-life.

Interleukin 1 augments the expression of the interleukin 2 receptor alpha-chain in interleukin 6-stimulated myeloid cells by a transcriptional and posttranscriptional mechanism.

We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6-induced IL-2R alpha expression in M1 cells.

Interleukin-4 inhibits interleukin-1 alpha-induced granulocyte-macrophage colony-stimulating factor gene expression in a murine B-lymphocyte cell line via downregulation of RNA precursor.

Interleukin-4 (IL-4) regulates the growth of B cells. When combined with colony-stimulating factors (CSFs) and selected cytokines, IL-4 has a synergistic effect on the clonal growth of bone marrow cells. Recently, we have shown that IL-1 alpha and lipopolysaccharide induce expression of the granulocyte-macrophage CSF (GM-CSF) gene in murine B-cell lines.

Transient expression of the IL-2 receptor alpha-chain in IL-6-induced myeloid cells is regulated by autocrine production of prostaglandin E2.

The alpha-chain of the interleukin 2 receptor (IL-2R alpha) is expressed on monocytes and macrophages after activation by bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). In the present study, we investigated whether the expression of IL-2R alpha is associated with the process of differentiation of myeloid cells to mature macrophages and how this expression is regulated. The murine myeloid M1 cell line, which can be induced by leukemia inhibitory factor (LIF) or interleukin 6 (IL-6) to differentiate from blast cells to mature macrophages, was used as a model system for myeloid differentiation.

Concanavalin A-induced granulocyte-macrophage colony-stimulating factor production in a murine T-cell line is posttranscriptionally controlled.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor (HGF) that regulates the proliferation and differentiation of cells of the myeloid lineage. It can be produced by a variety of cells. One of the major sources of GM-CSF is activated T cells, which transiently produce this HGF.

Correlation in the expression of type IV collagenase and the invasive and chemotactic abilities of myelomonocytic cells during differentiation into macrophages.

Monomyelocytic phagocytes originate in the bone marrow and while differentiating into macrophages migrate to inflammatory foci and target tissues by egress from the capillary blood vessels. During such diapedesis, the cells must traverse tissue barriers such as basement membrane, which has type IV collagen as its principal structural element. We studied whether the expression of type IV collagenase activity, invasion through basement membrane, and the response to inflammatory chemoattractants are related to each other and to the process of differentiation of murine M1 myeloid leukemia cells into macrophages.

Regulation of interleukin-4 receptors on murine myeloid progenitor cells by interleukin-6.

Interleukin-4 (IL-4) is a T-cell-derived cytokine that regulates induction of proliferation of resting B cells and acts on various other immunocompetent cells, such as monocytes/macrophages and mast cells, as well as hematopoietic progenitor cells. On hematopoietic progenitor cells, cooperation with another cytokine (such as granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, IL-3, or IL-6) is required to render the cells responsive to IL-4. The present study was undertaken to determine if such an interaction entails induction of IL-4 receptor (IL-4R) expression.

Identification of sequences within the murine granulocyte-macrophage colony-stimulating factor mRNA 3'-untranslated region that mediate mRNA stabilization induced by mitogen treatment of EL-4 thymoma cells.

Phorbol esters (TPA) and concanavalin A (ConA) are known to induce granulocyte-macrophage colony-stimulating factor (GM-CSF) production in murine thymoma EL-4 cells by mRNA stabilization. The role of the 3'-untranslated region (3'-UTR) in GM-CSF mRNA stabilization induced by TPA and ConA in EL-4 cells was examined by transfection studies using chloramphenicol acetyltransferase (CAT) constructions. The GM-CSF 3'-UTR contains a 63-nucleotide region at its 3' end with repeating ATTTA motifs which is responsible for mRNA degradation in a variety of cell types (Shaw, G.

IL-1 alpha induces granulocyte-macrophage colony-stimulating factor gene expression in murine B lymphocyte cell lines via mRNA stabilization.

IL-1 has been shown to induce granulocyte-macrophage (GM)-CSF production in several cell types including T lymphocytes, fibroblasts, and endothelial cells. We have previously demonstrated that bacterial LPS activates expression of the GM-CSF gene in murine B lymphocytes. Inasmuch as LPS is also an inducer of IL-1, we asked whether IL-1 could itself induce GM-CSF gene expression in B lymphocytes.

Post-transcriptional regulation of granulocyte-macrophage colony-stimulating factor synthesis in murine T cells.

The granulocyte-macrophage CSF (GM-CSF) gene is known to be controlled at a variety of levels in different cell types. We showed previously that GM-CSF production by lectin or phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate (TPA]-treated T cells was unaffected by cyclosporin A whereas IL-2 and IL-3 expression were. Cyclosporin A is thought to inhibit transcription that suggests that IL-2 and IL-3 are regulated primarily at the transcriptional level while GM-CSF is not.

Induction of interferon-beta and 2',5'-oligoadenylate synthetase mRNAs by interleukin 6 during differentiation of murine myeloid cells.

Interleukin 6 (IL 6) induces differentiation of murine myelomonocytic leukemia (M1) cells into mature macrophages. This process is monitored by the sequential appearance of surface markers, induction of intracellular enzymes, and changes in morphology as the cells progress from blast cells to mature macrophages. Differentiation is also associated with growth arrest and accumulation of the differentiating cells in the G0/G1 phase of the cell cycle.