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

Four members of the tumor necrosis factor (TNF) ligand family, TNF-alpha, LT-alpha, LT-beta, and LIGHT, interact with four receptors of the TNF/nerve growth factor family, the p55 TNF receptor (CD120a), the p75 TNF receptor (CD120b), the lymphotoxin beta receptor (LT beta R), and herpes virus entry mediator (HVEM) to control a wide range of innate and adaptive immune response functions. Of these, the most thoroughly studied are cell death induction and regulation of the inflammatory process. Fas/Apo1 (CD95), a receptor of the TNF receptor family activated by a distinct ligand, induces death in cells through mechanisms shared with CD120a. The last four years have seen a proliferation in knowledge of the proteins participating in the signaling by the TNF system and CD95. The downstream signaling molecules identified so far--caspases, phospholipases, the three known mitogen activated protein (MAP) kinase pathways, and the NF-kappa B activation cascade--mediate the effects of other inducers as well. However, the molecules that initiate these signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor receptor family.
 ...
PMID:Tumor necrosis factor receptor and Fas signaling mechanisms. 1035 62

Excessive production of the tumor necrosis factor (TNF) ligand-receptor system has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We therefore investigated the expression of TNF, lymphotoxin alpha (LTalpha), lymphotoxin beta (LTbeta), and their receptor (p55, p75, LTbeta-R) transcripts within the tumor tissue in different NHL histological subtypes. The constitutive expression of genes coding for TNF-related ligands and receptors was found in almost all 31 NHL samples studied. Semi-quantitative reverse transcription/polymerase chain reaction and computed densitometry assays revealed that the amounts of TNF, LTalpha, p55, and LTbeta-R mRNA were higher in follicular NHL than in other histological entities. Therefore tumor cell immunopurification was performed in representative follicular NHL samples and consistent results were obtained. The pattern of LTbeta gene expression was different from that of the other molecules, indicating the existence of distinct mechanisms of gene regulation. These results indicate that the transcription of genes coding for the TNF ligand-receptor system in NHL tumor tissue is more widespread than originally thought and that the heterogeneity of their expressions might be related to histological features. The expression of TNF-related ligands and receptors in tumor tissues is likely to contribute to the clinicopathological features of lymphoid-derived malignancies.
 ...
PMID:Expression of genes coding for the tumor necrosis factor and lymphotoxin ligand-receptor system in non-Hodgkin's lymphomas. 1109 13

Fracture healing is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Recent evidence for the role of tumor necrosis family members in the coupling of cellular functions during skeletal homeostasis suggests that they also may be involved in the regulation of skeletal repair. The expression of a number of cytokines and receptors that are of functional importance to bone remodeling (osteoprotegerin [OPG], macrophage colony-stimulating factor [M-CSF], and osteoprotegerin ligand [receptor activator of NF-kappaB ligand (RANKL)]), as well as inflammation (tumor necrosis factor alpha [TNF-alpha] and its receptors, and interleukin-1alpha [IL-1alpha] and -beta and their receptors) were analyzed over a 28-day period after the generation of simple transverse fractures in mouse tibias. OPG was expressed constitutively in unfractured bones and elevated levels of expression were detected throughout the repair process. It showed two distinct peaks of expression: the first occurring within 24 h after fracture and the second at the time of peak cartilage formation on day 7. In contrast, the expression of RANKL was nearly undetectable in unfractured bones but strongly induced throughout the period of fracture healing. The peak in expression of RANKL did not correlate with that of OPG, because maximal levels of expression were seen on day 3 and day 14, when OPG levels were decreasing. M-CSF expression followed the temporal profile of RANKL but was expressed at relatively high basal levels in unfractured bones. TNF-alpha, lymphotoxin-beta (LT-beta), IL-1alpha, and IL-1beta showed peaks in expression within the first 24 h after fracture, depressed levels during the period of cartilage formation, and increased levels of expression on day 21 and day 28 when bone remodeling was initiated. Both TNF-alpha receptors (p55 and p75) and the IL-1RII receptor showed identical patterns of expression to their ligands, while the IL-1R1 was expressed only during the initial period of inflammation on day 1 and day 3 postfracture. Both TNF-alpha and IL-1alpha expression were localized primarily in macrophages and inflammatory cells during the early periods of inflammation and seen in mesenchymal and osteoblastic cells later during healing. TNF-alpha expression also was detected at very high levels in hypertrophic chondrocytes. These data imply that the expression profiles for OPG, RANKL, and M-CSF are tightly coupled during fracture healing and involved in the regulation of both endochondral resorption and bone remodeling. TNF-alpha and IL-1 are expressed at both very early and late phases in the repair process, which suggests that these cytokines are important in the initiation of the repair process and play important functional roles in intramembraneous bone formation and trabecular bone remodeling.
 ...
PMID:Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. 1139 77

TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin-alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production. To distinguish between these possibilities, DCs were generated from bone marrow (BM) cultures prepared from wild-type (wt) and mutant mice in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield of CD11c(+) major histocompatibility complex (MHC) class II(+) DCs generated from TNF/LTalpha/LTbeta(-/-) BM culture was significantly reduced compared with wt BM culture. In order to further dissect the individual pathways responsible for defective DC properties observed in TNF/LTalpha/LTbeta(-/-) mice, the panel of TNF/LT ligand and receptor single KO mice were used. The production of DCs from BM culture was significantly reduced in TNF(-/-) and TNF receptor (TNFR) p55(-/-) mice, but normal in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice. Recombinant TNF (rTNF) exogenously added to TNF/LTalpha/LTbeta(-/-) BM cultures could reverse this defect, and blocking antibodies showed partial effect on BM cultures of wt mice. Conversely, numbers of mature DCs in spleen were significantly decreased in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice, but not in TNF(-/-) and TNFRp55(-/-) mice. These results reveal 2 distinct contributions of TNF/LT cytokines. First, TNF acting through TNF receptor is involved in the development/maturation of DCs in BM progenitor cultures, but this function appears to be redundant in vivo. Second, the microenvironment in peripheral lymphoid organs associated with LTalpha/LTbeta-LTbetaR signaling and chemokine production is critical for recruitment efficiency of DCs, and this pathway is indispensable.
 ...
PMID:Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo. 1256 Feb 41

Elevated tumor necrosis factor (TNF) and its soluble receptors (p55 and p75) plasma levels in patients with non-Hodgkin's lymphoma (NHL) have been shown to correlate with various adverse prognostic factors and predict poor NHL outcome. In vitro studies demonstrated that TNF expression level could be influenced by TNF-376, -308, -238, -163 promoters' polymorphisms. To explore whether these polymorphisms confer the susceptibility to and influence NHL outcome, we genotyped the TNF-376, -308, -238, -163 polymorphisms in 204 NHL patients and 96 healthy controls. The frequency and distribution of polymorphic alleles were similar in both studied groups. TNF-308A was the only polymorphic allele related to elevated TNF, p55, p75 plasma levels (p = 0.009, p = 0.03, p = 0.007, respectively), lower complete remission rate (p = 0.01), higher progression (p = 0.06) and death (p = 0.01) incidences. TNF-308A was the sole allele of independent prognostic significance for shorter freedom from progression (FFP) and overall survival (OS) (p = 0.009 and p = 0.017, respectively). These data indicate that innate immunity as reflected by the genetic propensity of the host to regulate TNF expression influences clinical course and outcome of NHL.
 ...
PMID:[The role of genetic polymorphisms within tumor necrosis factor promoter gene in non-Hodgkin's lymphomas]. 1678 63

The role of tumor necrosis factor (TNF)-308A polymorphic allele on non-Hodgkin's lymphoma (NHL) outcome was documented in the previous studies, although the role of the neighboring polymorphisms was unknown. The aim of the present study was to asses the frequencies and distributions of the HLA DRB1, TNF-308 and lymphotoxin alpha (LTalpha)+252 allelic polymorphisms in NHL patients and healthy controls and their influence on NHL outcome. The HLA DRB1, TNF-308 and LTalpha +252 allelic frequencies and distributions didn't differ significantly between patients and healthy controls, thus it is unlikely that polymorphisms within the above mentioned sites confer susceptibility for lymphoma occurrence. Among the polymorphic alleles HLA DRB1*03, TNF-308A and LTalpha +252A remaining in linkage disequilibrium, TNF-308A was the only allele associated with higher TNF and its p55 and p75 receptors' plasma levels (p = 0.009, p = 0.03, and p = 0.007), lower complete remission rates (p = .006), shorter freedom from progression (FFP) and overall survival (OS) (p = 0.009 and p = 0.017, respectively). Among the polymorphic HLA DRB1 alleles, null HLA DRB1*02 was the sole allele along with the TNF-308A that remained independent factors for shorter FFP (relative risk [RR] = 1.18, p < 0.02 and RR = 1.63, p < 0.0001, respectively) and OS (RR = 1.25, p < 0.0001 and RR = 1.51, p < 0.0001, respectively). Innate immunity reflected by inherited HLA DRB1 genes repertoire and genetic propensity of the host to regulate TNF production and/or other closely linked genes influences clinical course and outcome of NHL.
 ...
PMID:[The role of HLA DRB1 genetic polymorphisms in non-Hodgkin's lymphomas]. 1678 64


<< Previous 1 2