Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferons are proteins elaborated by infected cells that protect noninfected cells from viral infection. These proteins produce a temporary "antiviral state" by altering nucleotide metabolism and cytoplasmic enzyme induction. Interferons appear early after viral infection locally and systematically to limit spread of viral infection; they also affect cell differentiation, growth, surface, antigen expression, morphologic findings, and immunoregulation. Several human disorders have diminished interferon production. Newborns have normal interferon alpha but deficient interferon gamma production. Infants with congenital infections may also have defects in interferon production. Immunosuppressed patients receiving transplants (marrow, heart, of kidney) have diminished interferon production, particularly immediately after transplant. Deficiencies of interferon have also been noted in Down's syndrome, cellular immunodeficiencies, uremia, malnutrition, and hematopoietic malignancy. Leukocyte interferon has been of therapeutic value in herpes zoster infections, in patients with cancer, and in patients with hepatitis B infection. Interferon has not been proved to help children with congenital cytomegalovirus or rubella. Interferon can shrink lymphoid tumors, particularly non-Hodgkin's lymphoma.
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PMID:UCLA conference. Interferon: immunobiology and clinical significance. 617 66

Interleukin-10 (IL-10) is a pleiotropic cytokine produced by type 2 helper cells (Th2), as well as by monocytes and macrophages, and normal and neoplastic B lymphocytes. It is highly homologous to an open reading frame of Epstein-Barr virus (EBV) called BCRF1, and EBV infection of B-cells up-regulates IL-10. IL-10 production has strong immunosuppressive effects via inhibition of Th1 type cytokines, including interferon gamma and interleukin-2. On B-cells, IL-10 has a potent stimulating effect, inducing proliferation and differentiation. Interestingly, in cell lines derived from B-cell lymphomas, IL-10 production has been found to be up-regulated, and it serves as an autocrine growth factor. In patients with non-Hodgkin's lymphoma (NHL), serum IL-10 levels are significantly increased when compared to normal individuals and NHL patients in remission. The prognostic significance of these increased levels vary according to the assay used. Both human IL-10 and viral IL-10 are increased, and when specific assays for human IL-10 are used, there seems to be no prognostic significance, whereas when the assay cross-reacts with viral IL-10, high levels correlate with poor prognosis. These results suggest that viral IL-10 might have some pathogenic role in NHL.
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PMID:Interleukin-10 in non-Hodgkin's lymphoma. 932 87

Low-dose total-body irradiation (TBI) is used in the treatment of chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma. The usual practice is to give very low individual fractions (0.1 to 0.25 Gy) several times a week, to a total dose of 1.5 to 2 Gy. Despite this low dose, low-dose TBI can induce long-term remissions in the majority of patients. Immune enhancement, rather than direct radiation cell killing, is one of the suggested mechanisms by which low-dose TBI can exert its effect. Data from animal experiments have shown that low-dose TBI could enhance the immune response through (1) augmenting the proliferative reactive response of the T cells to mitogenic stimulation; (2) altering cytokine release, particularly the activation of interferon gamma and Il2 production; (3) increasing the expression of Il2 receptors on the T-cell surface; (4) facilitating signal transduction in T lymphocytes; (5) increasing splenic catecholamine content and lowering the serum corticosterone level; and (6) eliminating a particularly radiosensitive subset of the suppressor T cells. Data for humans, though scarce, suggest that at least some of these mechanisms occur in patients treated with low-dose TBI. Whether these immunomodulatory effects are responsible for the clinical outcome is not yet clear. Much is still unknown about the immunobiology of low-dose TBI, its clinical potential, and the possible synergism with chemotherapy, biological response modifiers, or immunotherapy. This lack of comprehensive knowledge hampers the optimal and widespread use of this intriguing and potentially useful treatment modality in clinical practice.
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PMID:The immunobiology of low-dose total-body irradiation: more questions than answers. 1079 Feb 82

The objectives of this study were to quantify colonic cytokine and endothelial cell adhesion molecule (ECAM) expression in the colons of severe combined immunodeficient (SCID) mice reconstituted with different subsets of CD4+ T lymphocytes. We found that animals injected with CD45RBhigh but not CD45RBlow T cells or phosphate-buffered saline (PBS) developed clinical evidence of colitis at 6-8 weeks following reconstitution, as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of a variety of Th1 and macrophage-derived cytokines including interferon gamma, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-12, and IL-18 lymphotoxin-beta. In addition, message levels and vascular surface expression of ICAM-1, VCAM-1, and MAdCAM-1 were all significantly enhanced in the colitic SCID mice reconstituted with CD45RBhigh T cells compared with SCID mice reconstituted with PBS or CD45RBlow T cells that did not develop disease. Significant increases in some of these ECAMs were also noted in the cecum and stomach and to a lesser degree in the small bowel. Our data confirm that reconstitution of SCID mice with CD45RBhigh but not CD45RBlow T cells induces chronic colitis, and that the colonic inflammation is associated with enhanced expression of proinflammatory cytokines and different ECAMs in the colon. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RBhigh T cells enhances ECAM expression in tissues distant from the site of active inflammation.
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PMID:Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+ T cells. 1096 89

The liver regenerates after acute injury via hepatocyte cell division; during chronic injury, when hepatocyte replication is impaired or blocked, liver progenitor oval cells mediate liver regeneration. If both regeneration options are blocked in animal models, then liver failure and death ensues. The mechanisms underlying oval cell induction, proliferation, and subsequent liver regeneration remain poorly characterized. In particular, cell-signaling pathways that distinguish the alternative pathways are unknown. This study shows that in a mouse model, hepatic expression of lymphotoxin-beta (LTbeta) and interferon gamma (IFNgamma) transcripts is increased in response to the choline-deficient, ethionine-supplemented (CDE) diet, which induces oval cell-mediated liver regeneration. Oval cells express LTbeta and IFNgamma transcripts, contributing to the increased expression in the liver of mice fed the CDE diet. An attenuated oval cell response to such a diet was observed in LTbeta receptor-, LTbeta-, and IFNgamma-gene targeted mice. Loss of LTbeta and LTbeta receptor signaling reduced the number of oval cells expressing A6 and muscle pyruvate kinase. The lack of IFNgamma signaling reduced muscle pyruvate kinase(+), but not A6(+), oval cells. In contrast, partial hepatectomy suppressed LTbeta and IFNgamma transcripts. We also show that IFNgamma induces STAT-3 phosphorylation in an oval cell line. In conclusion, LTbeta, LTbeta receptor, and IFNgamma are involved in oval cell-mediated, but not hepatocyte-mediated, liver regeneration, and the absence of these pathways impairs the oval cell-dependent regenerative response.
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PMID:Differential lymphotoxin-beta and interferon gamma signaling during mouse liver regeneration induced by chronic and acute injury. 1566 Mar 90

The molecular mechanisms of apoptosis caused by IFN-gamma (interferon gamma)/LIGHT (lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells) have not been studied in detail. The present study was undertaken to gain insights into the signaling pathways involved in apoptosis induced by IFN-gamma/LIGHT in hepatocellular carcinoma (HCC) cell lines. Cell proliferation assay, flow cytometry, Western blotting, gene transfer and RNA interference were used in this study. LIGHT enhanced IFN-gamma-mediated apoptosis in Hep3B cells. IFN-gamma/LIGHT-induced apoptosis was inhibited by blocking peptides to the lymphotoxin beta receptor (LT-beta R), and not by the herpes virus entry mediator (HVEM). Expression of LT-beta R remained unchanged after cytokine treatments. IFN-gamma/LIGHT treatment resulted in the down-regulation of Bcl-XL and the activation of caspase-9 and caspase-3 as well as the decrease of phosphorylation of STAT3. HepG2 and SMMC-7721 cells, which showed high levels of endogenous Bcl-XL, displayed resistance to IFN-gamma/LIGHT-induced apoptosis. Overexpression of Bcl-XL in Hep3B cells increased the resistance to IFN-gamma/LIGHT induced apoptosis while the down-regulation of Bcl-XL in HepG2 and SMMC-7721 cells by RNA interference decreased the resistance. Our study provides important mechanistic insights into IFN-gamma/LIGHT- induced apoptosis in HCC cells and may help to select better therapeutic strategies for certain cancers with distinct Bcl-XL expression.
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PMID:Expression level of Bcl-XL critically affects sensitivity of hepatocellular carcinoma cells to LIGHT-enhanced and interferon-gamma-induced apoptosis. 1739 46