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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratinocytes immortalized by human papillomaviruses (HPV) 16 and 18 are partially resistant to the inhibition of proliferation exerted by transforming growth factor-beta (TGF-beta). To determine if this finding reflects a generalized resistance to inhibitory cytokines, we studied the effect of tumor necrosis factor-alpha (TNF-alpha) on subconfluent cultures of both normal and HPV-immortalized human foreskin keratinocytes. Whereas primary and HPV-16-immortalized keratinocytes were sensitive to TNF-alpha, HPV-18-immortalized keratinocytes (and those immortalized by simian virus 40) were resistant to the inhibitory effects of this cytokine. The ability of HPV-18 to induce a more resistant phenotype correlated with its more potent in vitro transforming activity and its apparent association with more aggressive tumors. Interestingly, the state of TNF-induced growth inhibition in normal or HPV-16-immortalized keratinocytes was not accompanied by a reduction in the expression of c-myc RNA or protein. This contrasts sharply with the ability of TGF-beta to inhibit c-myc RNA expression in normal cells. Evidently, the resistance of HPV-immortalized keratinocytes to TNF-alpha and TGF-beta proceeds along different regulatory pathways.
Mol Carcinog 1992
PMID:Differential effect of tumor necrosis factor on proliferation of primary human keratinocytes and cell lines containing human papillomavirus types 16 and 18. 132 69

The immunogenic regions of human Tumor Necrosis Factor alpha (huTNF) have been mapped by studying the interaction between various mouse anti-huTNF sera and synthetic huTNF fragments, spanning the entire sequence of huTNF. Three main immunogenic regions were identified within residues 1-23, 95-116 and 137-157 of huTNF and two other less immunogenic regions within residues 117-136 and 37-55. The same huTNF regions were found to contain antigenic sites by binding studies with cognate anti-peptide sera. Competitive binding experiments with shorter synthetic subfragments provided evidence for the location of strong antigenic sites within residues 1-10, 17-23, 104-112 and 137-143. In particular the immunodominant site was found to be located within residues 104-112. huTNF regions corresponding to residues 24-36, 56-75, 76-94, and 147-157 resulted to be not or poorly antigenic. However, treatment of huTNF with Triton X-100 under conditions that partially dissociate the oligomeric quaternary structure resulted in the exposition of sites recognized by sera against peptides huTNF [56-75] and huTNF [76-94], suggesting that antigenic sites not accessible in the oligomeric huTNF are exposed in the dissociated form. The principal antigenic sites in the oligomeric molecule are localized in the flexible N-terminal part and in hydrophilic segments located in the "middle/top" region of the molecule, opposite to the C-terminus. Protein segments of the "bottom" region, close to the C-terminus, were poorly immunoreactive. Neutralization assays of TNF cytolytic activity on L-M cells showed that binding of antibodies to epitopes located in the "middle/top" regions of huTNF does not affect its cytolytic activity, supporting the hypothesis of a receptor binding site location at the "bottom" of TNF trimer.
Mol Immunol 1992 Apr
PMID:Antigenic regions of tumor necrosis factor alpha and their topographic relationships with structural/functional domains. 137 65

Intravenous administration of a single dose (20 micrograms) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats decreased the rate of intestinal glucose absorption. In vivo, the oxidation of [U-14C]glucose to 14CO2 was significantly increased by the cytokine. In addition, [14C]lipid accumulation from [U-14C]glucose was increased both in liver and brown adipose tissue of the TNF-injected animals. The decrease observed in intestinal glucose absorption was not associated with changes in intestinal metabolism. There was no difference in glucose metabolism by isolated enterocytes from either control or TNF-injected rats whether in the absence or presence of different concentrations of the cytokine in the incubation medium. In contrast, tumour necrosis factor altered the rate of gastric emptying as measured by the gastrointestinal distribution of 3[H]inulin following an intragastric glucose load. These results suggest that the cytokine profoundly alters glucose metabolism by increasing its whole-body oxidation rate and delaying intestinal absorption through a reduced gastric emptying.
Mol Cell Biochem 1992 May 13
PMID:Effects of tumour necrosis factor-alpha (cachectin) on glucose metabolism in the rat. Intestinal absorption and isolated enterocyte metabolism. 151 34

Tumour necrosis factor alpha (TNF-alpha) has been shown to be the principal mediator of Gram-negative bacterial endotoxin-induced shock. Nevertheless, evidence suggests that TNF-alpha plays a beneficial role in controlling bacterial infections when multiplication of the microorganism is required to kill the host. Using an infant rat model of Neisseria meningitidis infection, we found that blood TNF-alpha concentration reaches a peak three hours after intraperitoneal injection of 3 x 10(6) bacteria. Thereafter, the level of TNF-alpha decreased and was undetectable six to eight hours after infection. A correlation was observed between the magnitude of initial TNF-alpha response and a fatal outcome. Pretreatment of the animals with polyclonal anti-TNF antiserum significantly reduced mortality relative to animals pretreated with control serum. However, pretreatment of animals with anti-TNF antibody did not alter the bacterial invasion of the cerebrospinal fluid. Injection of heat-killed bacteria did not cause death and induced lower TNF-alpha levels than the same number of live bacteria. This excludes the possibility that the role of TNF-alpha is to mediate a shock induced by the endotoxin component of the bacterial inoculum. These results indicate that TNF-alpha has a deleterious effect in this model of bacteraemia. Identification of the critical factors that determine the action of TNF-alpha during lethal bacteraemia will lead to a better understanding of these diseases and the development of appropriate therapeutic intervention.
Mol Microbiol 1992 Mar
PMID:Tumour necrosis factor alpha antibody protects against lethal meningococcaemia. 155 59

To evaluate the feasibility of tumor necrosis factor-alpha (TNF-alpha) treatment of lung cancer patients, we chose the malignant cells contained in their pleural effusions as a first convenient target. We found, however, that a TNF-alpha inhibitor (TNF-alpha I) activity was present in both patient sera and pleural fluids. We therefore compared the TNF-alpha I activity present in patients with benign or malignant pleural effusions using a bioassay of TNF-alpha inhibition and partially characterized it. A high TNF-alpha I activity characterizes cancer patients with sera levels twice as high as the control level measured for blood bank donors (2.54 +/- 1.28 versus 1.19 +/- 0.38) and with even higher levels in pleural fluids (3.75 +/- 1.83). In contrast, patients with benign pleural effusions present similar levels of TNF-alpha I activity, at about the control level, in both their sera and pleural fluids (1.37 +/- 0.98 versus 1.16 +/- 0.85). A high TNF-alpha I activity is consistently found in cancer patients but is only released in vitro by leukocytes. It is most likely related to recently purified TNF-alpha inhibitors that, as soluble shed fragments of TNF receptors, may function as traps for TNF molecules. This study suggests that tumors may evade TNF cytotoxic action by modulating systemic levels of TNF and implies a reassessment of TNF therapy in cancer patients.
Am J Respir Cell Mol Biol 1992 May
PMID:Characterization of a tumor necrosis factor-alpha inhibitor activity in cancer patients. 158 Oct 74

The inflammatory cytokines tumour necrosis factor-alpha (TNF alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus. Furthermore, IL-6 is produced by some anterior pituitary cells suggesting a paracrine/autocrine role for this cytokine. We show that TNF alpha induces dispersed ovine pituitary cells to produce increased levels of growth hormone (GH) and IL-6 mRNA and secreted IL-6 in a dose and time dependent manner. TNF alpha at concentrations between 1-1000 U/ml increased GH and IL-6 mRNA, relative to control levels, by 5 h post-stimulation. For IL-6, TNF alpha increased specific mRNA at 5 h and 12 h but not 24 h post-stimulation. TNF alpha also induced secreted IL-6 to levels above that spontaneously secreted at all time points from 5 h to 48 h. Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH beta) subunit mRNA were unaffected by TNF alpha. We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells. The implications for paracrine/autocrine control of pituitary hormone synthesis in acute and chronic disease are discussed.
Mol Cell Endocrinol 1992 Mar
PMID:Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells. 163 12

Tumor necrosis factor, TNF, is a 17-kDa protein secreted by macrophages and classified as a cytokine. TNF binds to high-affinity receptors on the cell surface and is involved in a wide variety of biological responses. There are at least two types of receptors, tumor necrosis factor receptors 1 and 2 (TNFR1 and TNFR2). The genes for TNFR1 a 55-kDa protein, and TNFR2, a 70-kDa protein, have been mapped to human chromosomes 1 12 (12pter-cen) and (1pter-p32), respectively, by Southern blot analysis of human x Chinese hamster somatic cell hybrid panels. Recently, the corresponding genes in the mouse have been mapped to chromosomes 4 and 6 in regions that are conserved on human chromosomes 1 and 12.
Somat Cell Mol Genet 1991 Sep
PMID:Tumor necrosis factor receptor genes, TNFR1 and TNFR2, on human chromosomes 12 and 1. 166 15

The hepatic response to systemic injury is characterized by a co-ordinated increase in the expression of several, functionally essential plasma proteins. The factors responsible for initial hepatic stimulation have been identified and include the cytokines IL-1 (interleukin-1), tumor necrosis factor alpha (TNF alpha), IL-6 (interleukin-6), hepatocyte-stimulating factor-III (HSF-III) as well as corticosteroids. The absolute level of expression of the regulated proteins appears to be modulated by the pre-existing hepatic hormonal environment and changes to that environment that occur during acute phase reactions. The specific effects of glucocorticoids, IL-1 and activation of protein kinase C are addressed in this study. In order to predict the phenotype of liver response in acute phase, the hepatic activities of all inflammatory cytokines present must be established. Moreover, it must be recognized that the hepatic environment itself can modulate the anabolic response of the liver to these cytokines. The same considerations are needed when determining the changes seen during the progression to chronic inflammation.
Mol Biol Med 1990 Apr
PMID:Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation. 169 52

A number of investigators have demonstrated the association of CD5+ (Ly-1/Leu-1) B cells with autoimmunity, excessive B-cell proliferation, and transformation. Previous work from our laboratory, among others, suggests that the selective advantage of this frequently autoreactive B-cell subset is to provide activation signals to conventional antigen-specific B cells. If one current hypothesis is correct then the overrepresentation of CD5+ B cells in some diseases and their novel capacity to act as helper cells reflect the activities of a separate B-cell lineage. Because of these observations it is of particular interest to evaluate the factors which contribute to the maturation of the CD5+ B-cell subset. The possibility that CD5+ B cells produce a factor or factors capable of influencing their own development was the focus of the present investigation. Rather than attempt to obtain soluble factors from heterogeneous CD5+ B-cell populations which could be contaminated with cytokine secreting monocytes or which could require as yet undefined activation signals in order to secrete putative factors, we chose to evaluate the production of CD5+ B-cell inducing factor(s) by monoclonal CD5+ B-cell hybridomas. Added incentive to this approach was provided by the observation that these hybridomas elaborate a factor(s) which, together with (NPb) idiotype-specific antibody produced by the hybridoma, substitutes for CD5+ B-cell populations in activating antigen-specific (NPb idiotypic) B cells in vitro. Furthermore, because of the low percentage of CD5+ B cells in the spleen and their relatively low level of CD5 antigen expression, we employed a sensitive functional assay rather than surface antigen expression alone to detect small numbers of mature CD5+ B helper cells. With this previously described system it was possible to observe the induction of functional CD5+ B cells following a 40 h culture of apparently CD5- B-cell populations with a 19-22 kd factor or factors derived from a CD5+ B hybridoma. Data presented here and elsewhere suggest that this CD5+ B-cell inducing activity is not mediated by IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, GM-CSF, or TNF. The role that such a B cell derived, B-cell directed factor may play in immunity and disease is discussed.
J Mol Cell Immunol 1990
PMID:A CD5+ B cell hybridoma derived factor(s), which induces maturation of CD5+, idiotype-specific B-cell populations. 169 80

No correlation exists in HL60 cells between NF-kappa B activation by tumor necrosis factor (TNF alpha) and TNF beta and intracellular levels of cyclic AMP. Cyclic AMP levels did not increase upon treatment of cells with each of these cytokines, although NF-kappa B was activated. Forskolin or 1-isobutyl-3-methylxanthine drastically increased intracellular levels of cyclic AMP, but neither activated NF-kappa B nor influenced TNF-induced NF-kappa B activation.
Mol Cell Biol 1991 Apr
PMID:Cyclic AMP-independent activation of transcription factor NF-kappa B in HL60 cells by tumor necrosis factors alpha and beta. 170 75


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