Disease relevance of TNF

• Fresh B cells from cows with persistent lymphocytosis constitutively transcribed TNF, LT-alpha and TGF-beta1 mRNAs [1].
• When cytokine expression by macrophages incubated with M. avium subsp. paratuberculosis was compared to those of macrophages incubated with M. avium subsp. avium, M. avium subsp. paratuberculosis-infected cells showed greater expression of IL-10 (6 and 24 h) and less expression of TNF-alpha (6 h) [2].
• A subpopulation of calves, herein termed "hyperresponders" (HPR), was identified and defined by the patterns of plasma TNF-alpha concentrations that developed following two challenges with endotoxin (LPS, 0.8 mug Escherichia coli 055:B5 LPS/kg(0.75) live body wt) separated by 5 days [3].
• We previously reported that tumor necrosis factor alpha (TNF-alpha) was one of the cytokines that contributed to the leukemogenesis caused by bovine leukemia virus (BLV) [4].
• These data suggest that an aberrant expression of TNF-alpha might contribute to the progression of bovine leukosis in animals which develop persistent lymphocytosis of B-cells or B-cell lymphosarcoma [4].

Psychiatry related information on TNF

• A time study indicated that TNF-alpha mRNA concentrations peaked 3 h after endotoxin and virus induction of BAMs [5].

High impact information on TNF

• In vitro, TNF-alpha stimulates chemotaxis of bovine adrenal capillary endothelial cells and induces cultures of these cells grown on type-1 collagen gels to form capillary-tube-like structures [6].
• We show here that tumour necrosis factor-alpha (TNF-alpha), a secretory product of activated macrophages that is believed to mediate tumour cytotoxicity, is a potent inducer of new blood vessel growth (angiogenesis) [6].
• In vivo, TNF-alpha induces capillary blood vessel formation in the rat cornea and the developing chick chorioallantoic membrane at very low doses [6].
• The angiogenic activity produced by activated murine peritoneal macrophages is completely neutralized by a polyclonal antibody to TNF-alpha, suggesting immunological features are common to TNF-alpha and the protein responsible for macrophage-derived angiogenic activity [6].
• The mechanisms underlying this change in the affinity of endothelium for TNF were studied in four settings [7].

Chemical compound and disease context of TNF

• Results of our study indicate that PAF- and TNF-alpha-induced changes in neutrophil deformability and size may cause integrin- and selectin-independent trapping of neutrophils in the lungs of cattle with pneumonic pasteurellosis [8].
• Bovine macrophages, when exposed to P. levii or E. coli LPS, produced mRNA for TNF-alpha, IL-1beta, and IL-8 [9].
• Fetal responses to maternal endotoxemia consisted of increased ACTH and cortisol concentrations with delayed increases in PGE(2); TNF did not change in fetal fluids following maternal endotoxemia [10].
• Increase in blood glucose concentration at 1 hour after administration of E and TNF was followed by prolonged hypoglycemia that lasted through 6 hours [11].
• Both drugs, flumetasone and meloxicam, influenced TNF production in ex vivo cultures of blood and BAL cells, inhibiting excessive TNF production induced by local lung inflammation [12].

Biological context of TNF

• Finally, Dok-4 enhanced TNF-alpha-mediated NF-kappaB activation, whereas this was inhibited by transfection with Dok-4 small interfering RNA [13].
• To determine if the spontaneous cell proliferation observed in the late disease stages, such as persistent lymphocytosis and lymphosarcoma, correlated with the expression level of TNF-alpha, we analyzed the mRNA expression levels for TNF-alpha in spontaneously proliferating PBMCs derived from BLV-infected cattle [4].
• Our results indicate that HSP72 is upregulated in cultured bovine OL by heat stress but not by oxidative stress or cytokines such as IL-1 and TNF [14].
• Brief pretreatment of bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha) inhibited the above described FSS- or insulin-stimulated protein phosphorylation events and almost totally inhibited FSS- or insulin-stimulated NO production [15].
• Cerivastatin prevented TNF-alpha-induced downregulation of eNOS protein expression in a concentration-dependent manner (10(-8) to 10(-5) M) [16].

Anatomical context of TNF

• An inverse correlation between the level of pathology and bacterial load within the lymph node and the expression of IL-4, IL-10 and TNF was also observed [17].
• We evaluated the dynamic secretion of interleukin (IL)-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha) as well as phagosome acidification and organism killing at several time points after in vitro infection of bovine monocytes with M. avium subsp. paratuberculosis [18].
• Tumor necrosis factor-alpha (TNF alpha) inhibits progesterone and estradiol-17beta production from cultured granulosa cells: presence of TNFalpha receptors in bovine granulosa and theca cells [19].
• A similar degree of stimulation was achieved by supernatants from osteoblasts incubated with TNF before addition to osteoclasts, compared with supernatants to which TNF were added after osteoblast incubation [20].
• Incubation with PAF and TNF induced an increase in size of neutrophils [21].

Associations of TNF with chemical compounds

• These data suggest a role for mitochondrial Dok-4 as an anchoring molecule for the tyrosine kinase c-Src, and in turn as a regulator of TNF-alpha-mediated ROS production and NF-kappaB activation [13].
• Incubation of neutrophils with PAF and ZAP but not TNF, IL-8, LPS, or leukotoxin, resulted in decreased neutrophil deformability and increased F-actin content [21].
• The reduced expression of eNOS protein by TNF-alpha was also prevented by coincubation with cycloheximide [16].
• TNF-alpha stimulated the translocation of nuclear factor-kappaB (NF-kappaB), an effect that was not modified by cerivastatin [16].
• Furthermore, an inhibitor of NF-kappaB translocation, pyrrolidine dithiocarbamate failed to modify both the downregulation of eNOS expression and the increased binding activity of the cytosolic proteins to 3'-UTR of eNOS mRNA by TNF-alpha [16].

Regulatory relationships of TNF

• These proteins may play a role in TNF-alpha-induced eNOS mRNA destabilization [22].
• Although PAF and IL-8 inhibited TNF-alpha-induced ROS production in neutrophils adhered to collagen, fibronectin, and laminin, PAF enhanced ROS production strongly in HSP-adherent cells [23].
• DISCUSSION: TNF-alpha induces apoptosis in cultured cerebral endothelial cells through the cleavage of caspase-3 [24].
• A concentration of CRP similar to that detected in patients with cardiovascular risk (10 microg/ml) failed to modify the generation of superoxide anion stimulated by TNF-alpha [25].
• However, while merozoites plus IFN-gamma induced TNF-alpha mRNA expression in MDM, NO was not produced [26].

Other interactions of TNF

• Enhanced SEMA5A induces expression of at least nine genes related to the host's immune response, including TNF-alpha and IL-8 [27].
• Variables measured included expression of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-10, IL-12, transforming growth factor-beta, and suppressor of cytokine signaling-3 (SOCS-3); apoptosis of monocytes; acidification of phagosomes; and killing of MAP [28].
• Although IL-2 mRNA expression in ConA-stimulated PBMC from newborn calves was weaker than that in those from adult cows of ConA-stimulated controls, the expression levels became comparable after pretreatment with IL-1beta, TNF-alpha or IFN-gamma [29].
• Tumor necrosis factor alpha (TNF-alpha), which destabilizes eNOS mRNA, increased the binding activity of the cytosolic proteins in a time-dependent manner [22].
• RT-PCR analysis of cytokine expression by T cell lines which were dominated by gammadelta T cells revealed expression of IFN-gamma, TNF-alpha, TNF-beta, IL-2Ralpha transcripts [30].

Analytical, diagnostic and therapeutic context of TNF

• Quantitation of the cytokines TNF-alpha, IL-8 and IL-10 in bovine milk using real-time TaqMan PCR [31].
• Among the agents likely to be present in such supernatants are monocyte-derived tumor necrosis factor (TNF-alpha) and lymphocyte-derived tumor necrosis factor (TNF-beta) (lymphotoxin), both of which have recently been shown to stimulate bone resorption in organ culture [20].
• Finally, the WEHI 164 (clone 13) bioassay was used to show that Lkt/LPS synergism resulted in enhanced secretion of biologically active TNF-alpha [32].
• Northern blot analysis of total RNA showed that P. haemolytica induced early, abundant, and consistent synthesis of IL-1, TNF-alpha, and IL-8 mRNA [33].
• METHOD: The effects of TNF-alpha, IL-1beta, IL-6, and IL-8 were tested using cell viability assay, DNA fragmentation analysis (DNA laddering), Western blot analysis (Anti-poly-(ADP-ribose) polymerase [PARP] antibody), and caspase-3 activity [24].

References