Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron increases the synthesis of the iron-storage protein, ferritin, largely by promoting translation of preexisting mRNAs for both the H and L ferritin isoforms (H, heavy, heart, acidic; L, light, liver, basic). We have recently cloned and sequenced a full-length cDNA to murine ferritin H and identified ferritin H as a gene induced by tumor necrosis factor alpha (TNF-alpha, cachectin). Using primary human myoblasts, we have now examined the relationship between TNF-alpha and iron in regulating ferritin. Four lines of evidence suggest that TNF-alpha regulates ferritin independently of iron. First, evaluation of mRNA showed that TNF-alpha increased ferritin H chain specifically, provoking no change in steady-state levels of ferritin L mRNA; iron, in contrast, increased the mRNA of both isoforms. Second, the increase in ferritin H protein synthesis observed during TNF-alpha treatment was dependent on an increase in ferritin H mRNA: actinomycin D blocked the TNF-alpha-induced changes in ferritin H but did not inhibit the translational induction of ferritin seen with iron treatment. Third, equal ferritin mRNA induction was observed in iron-loaded cells and in cells depleted of iron by a permeant chelator, 2,2'-dipyridyl. Fourth, ferritin H induction by TNF-alpha and iron was additive over the entire range of iron concentrations, even at TNF-alpha doses known to maximally stimulate ferritin H mRNA levels. Nonetheless, the role of iron in translational regulation of ferritin was retained in TNF-alpha-treated cells; effective biosynthesis of TNF-alpha-induced, H-subunit-predominant ferritin protein required iron and could be enhanced by treatment of the cells with additional iron or blocked by 2,2'-dipyridyl. Finally, we observed that the TNF-alpha-mediated increase in ferritin synthesis peaked at 8 hr and was followed by a decrease in both H and L isoferritin synthesis; the addition of iron, however, reversed the late-occurring depression in ferritin synthesis. This suggests that TNF-alpha-induced synthesis of H-rich ferritin may reduce the regulatory pool of intracellular iron, secondarily inhibiting iron-mediated translation of ferritin mRNA. We conclude that TNF-alpha acts independently of iron in its induction of ferritin H mRNA but requires the presence of iron for this effect to be fully expressed at the protein level.
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PMID:Iron-independent induction of ferritin H chain by tumor necrosis factor. 205 77

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
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PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

Cachectin/tumor necrosis factor-alpha (TNF), a protein produced by macrophages upon stimulation, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in chronic infectious diseases. In order to study further the potential role of TNF in infectious diseases, a homologous system was employed in which recombinant Escherichia coli (E. coli) derived bovine TNF (rBoTNF) was injected in cattle, either as a single bolus or in a repetitive treatment-regime. No clinical signs were observed, although changes occurred in hematologic and immunologic parameters when less than 0.5 mg of TNF/100 kg body weight was administered twice daily for 18 days. Prolonged treatment with 0.05-0.5 mg/100 kg induced histologic but no gross changes in the kidneys and liver. When doses were increased above 0.5 mg/100 kg, depression, anorexia, cachexia, and diarrhea appeared rapidly. Pathologic changes were apparent in various tissues including liver, kidneys, and lymphoid organs; body fat depots were depleted. Most of these changes appeared to be reversible; return to normal tissue-morphology occurred within 3 weeks of withdrawal of rBoTNF. The clinical and pathologic changes induced by prolonged rBoTNF administration resembled those observed in some chronic parasitic and viral infections of cattle in which macrophage-activation characteristically occur. Our finding may be relevant to the elucidation of the pathogenesis of these and other chronic infections.
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PMID:Effect of chronic administration of recombinant bovine tumor necrosis factor to cattle. 260 27

1. Myocardial dysfunction during septic shock is associated with enhanced production of cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha). These cytokines depress cardiac mechanical function by a mechanism which is not well defined. 2. Bacterial endotoxin or cytokines cause the expression of Ca(2+)-independent nitric oxide (NO) synthase in cardiac myocytes, vascular endothelial cells and endocardial endothelial cells, causing enhanced production of NO. As NO has negative inotropic actions on cardiac muscle, we tested the sum effects of IL-1 beta plus TNF-alpha in the intact heart to determine whether enhanced expression of NO synthase activity in the cells that comprise the heart is involved in cardiac depression associated with cytokine stimulation. 3. Rat isolated working hearts perfused with IL-1 beta plus TNF-alpha showed a markedly greater depression in contractile function, measured as cardiac work, after 2 h of perfusion compared with time-matched control hearts. The depressant action of IL-1 beta plus TNF-alpha was first apparent after 1 h of perfusion; no early (15 min) cardiac depressant actions were seen. 4. The competitive inhibitor of Ca(2+)-dependent and Ca(2+)-independent NO synthases, NG-nitro-L-arginine methyl ester (L-NAME, 3 microM) when given concurrently with IL-1 beta plus TNF-alpha prevented the loss in contractile function such that these hearts after 2 h of perfusion had similar function to time-matched controls. L-NAME did not acutely reverse the loss of contractile function in hearts exposed for 2 h to IL-1 beta plus TNF-alpha. The protective action of L-NAME in the presence of cytokines was concentration-dependent and was not seen at a higher concentration (10 micro M) due to the significant reduction in coronary flow observed at this concentration.5. In contrast, when L-NAME (3 micro M) was given in the absence of IL-l beta plus TNF-alpha it depressed contractile function over the 2 h perfusion period by significantly reducing coronary flow.6. Inhibition of protein synthesis with cycloheximide (Cx) abolished the loss in function that occurred over 2h in both control and IL-1 beta plus TNF-a-treated hearts.7. Inducible, Ca2+-independent NO synthase activity was not observed in freshly isolated hearts but was observed in control hearts perfused for 2 h in vitro and was doubled in hearts perfused with IL-1 beta plus TNF-a. Cx prevented the expression of Ca2+-independent NO synthase in both control and cytokine-treated hearts.8. In summary, these results suggest that the depression of myocardial function by IL-l beta plus TNF-alpha is mediated, at least in part, by induction of Ca2+-independent NO synthase activity in the heart.
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PMID:The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. 753 96

Involuntary weight loss is a common finding and one associated with increased morbidity and mortality, especially in the elderly patient. The precise mechanisms by which weight loss occurs are currently being elucidated and probably involve the actions of classic hormones as well as cytokines, such as TNF (cachectin), adipsin, and interleukin-1 and interleukin-6. The differential diagnosis of involuntary weight loss is extensive, but case studies indicate that cancer, depression, and disorders of the gastrointestinal tract may be the most common causes. In approximately 25% of cases, no cause of weight loss is found despite extensive evaluation and prolonged follow-up. In the majority of cases, history, physical examination, and limited laboratory and radiologic studies reveal the cause of weight loss, when a cause is to be found. If an initial evaluation does not identify a cause, careful follow-up rather than undirected diagnostic testing is recommended. In the treatment of patients with involuntary weight loss, the underlying medical or psychiatric cause of the weight loss should be treated first if possible. Several medications are currently being investigated for treatment of patients with weight loss.
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PMID:Involuntary weight loss. 787 92

Every clinician knows the elevation of acute phase proteins at the inflammatory status, but nobody knows the CRP or SAA induction mechanism on inflammation, in which a lot of cytokines or chemokines are activated. Induction mechanism of CRP and SAA is analyzed based on the result of the normalization of serum CRP or SAA in rheumatoid arthritis by the IL-6 blocking therapy with a humanized anti IL-6 receptor antibody. Ultimately, IL-6 is a pivotal cytokine among IL-6, IL-1 and TNF-a in induction of CRP and SAA in hepatocyte. Furthermore, activation of STAT3, a transcriptional factor under IL-6 signal transduction pathway, is critical on the expression of these mRNAs. Based on this mechanism, the depression of CRP and SAA induction could be explained by the IL-6 blockage both in vitro and in vivo. Therefore, IL-6 blocking therapy may elucidate the pathogenic significance of IL-6 in chronic inflammatory disease.
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PMID:[Pathogenic analysis of chronic inflammatory disease based on the clinical results by IL-6 blocking therapy]. 1844 13

Psychiatric morbidity is common in rheumatoid arthritis (RA) patients and may affect disease activity and immunological markers. We studied the relationship of the psychiatric morbidity and immunological factors; the serum levels of Interleukin-1beta (IL-1beta), Tumor Necrosis Factor Alpha (TNF-alpha), Interleukin-18 (IL-18) and its inducer interleukin-12 (IL-12), and their impact on RA disease activity. Forty-two RA patients and 20 apparently healthy individuals as a control group were included in this study. Psychiatric morbidity was identified according to the International Classification of Disease, tenth version criteria (ICD-10). The Hospital Anxiety and Depression Scale (HADS) and the mental health Short Form 36 (SF-36) were applied for further analysis. Serum IL-1beta, IL-12, IL-18 and the TNF-a were measured using Enzyme-Amplified Sensitivity Immunoassays (EASIA) and were correlated with psychiatric morbidity and disease activity as measured by Health Assessment Questionnaire and Overall Status. Psychiatric morbidity was found in 40.48% of the studied patients, the most common psychiatric disorders among RA patients were depressive disorders and anxiety disorders. The SF-36 score was closely correlated to the anxiety and depression score (P < 0.001). RA patients showed high levels of IL-1beta, IL-12, IL-18 and TNF-alpha than the control group. There was a significant correlation between psychiatric morbidity, serum levels of IL-1beta, IL-12, IL-18, TNF-alpha and disease activity measurements. We have to view rheumatoid arthritis as a psycho-immumological disorder rather than an autoimmune disease. Furthermore, the studied cytokines may be a novel target for therapeutic intervention of rheumatoid arthritis and its psychiatric morbidity.
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PMID:Psychiatric morbidity associated with some cytokines (IL-1beta, IL-12, IL-18 and TNF-alpha) among rheumatoid arthritis patients. 2030 65

The prevalence of depression among patients diagnosed with cancer is higher than general population and is associated with faster tumor progression and shorter survival time. Cytokines whose primary function is to act as signaling molecules of the immune system have recently also been implicated in the pathogenesis of depression. The aim of present study was to investigate the relation between pro-infammatory cytokines [Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha)], depression and stressful life events in patients with acute leukemia. Twenty eight patients (18 males and 10 females) suffering from acute leukemia participated in this study. Their mean age was 33.3 +/- 12.1 years. They were subjected to psychiatric assessment using The Beck Depression Inventory (BDI), Holmes and Rahe Social Readjustment Scale, The Perceived Stress Scale (PSS) and The Brief Fatigue Inventory (BFI). Measurement of IL-6 and TNF-a genes expression in peripheral blood mononuclear cells was done using real-time PCR. Results revealed statistically significant elevation in the level of IL-6 gene expression, fatigue and perceived stress among depressed patients compared to none depressed group. The same results were obtained when comparing patients exposed to moderate or severe stressful life events compared to those exposed to none or mild stressful life events. Although, TNF-a gene expression was not associated with depression or stressful life events, it was associated with acute myeloblastic leukemia (AML). IL-6 gene expression was much higher among patients with AML than acute lymphoblastic leukemia (ALL), but the difference did not reach statistical significance. These findings support the hypothesis that IL-6 might be involved in the etiology and symptomatology of depression in cancer patients. The development of biologic therapies targeting IL-6 may raise the possibility of simultaneously countering the severe effects of depression.
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PMID:Pro-inflammatory cytokines and depression in patients with acute leukemia. 2030 66

Psoriasis is a chronic, genetic, inflammatory skin disease affecting approximately 2% of the population worldwide. Over the past decade, multiple studies have shown that not only is there an association between psoriasis and psoriatic arthritis, depression, and substance abuse, but psoriasis patients also have a higher incidence of obesity, diabetes, heart disease and stroke. In addition, and more concerning, young psoriatic patients particularly those with more severe disease are at an increased mortality risk even when controlling for these factors. The systemic inflammation in psoriasis generates elevation of C-reactive protein, homocysteine, and inflammatory cytokines such as TNF-a, IL-6, IL-17, IL-20, IL-22, and IL-23, which may contribute to the overall morbidity and mortality in these patients. Within this article we will discuss the associations between psoriasis and multiple systemic health problems.
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PMID:Psoriasis: comorbidities and associations. 2131 53

Depressive disorders have complex and multi-faceted underlying mechanisms, rendering these disorders difficult to treat consistently and effectively. One under-explored therapeutic strategy for alleviating mood disorders is the targeting of microRNAs (miRs). miRs are small non-coding RNAs that cause sequestration/degradation of specific mRNAs, thereby preventing protein translation and downstream functions. miR-155 has validated and predicted neurotrophic factor and inflammatory mRNA targets, which led to our hypothesis that miR-155 deletion would modulate affective behaviors. To evaluate anxiety-like behavior, wildtype (wt) and miR-155 knockout (ko) mice (littermates; both male and female) were assessed in the open field and on an elevated plus maze. In both tests, miR-155 ko mice spent more time in open areas, suggesting they had reduced anxiety-like behavior. Depressive-like behaviors were assessed using the forced swim test. Compared to wt mice, miR-155 ko mice exhibited reduced float duration and increased latency to float. Further, although all mice exhibited a strong preference for a sucrose solution over water, this preference was enhanced in miR-155 ko mice. miR-155 ko mice had no deficiencies in learning and memory (Barnes maze) or social preference/novelty suggesting that changes in mood were specific. Finally, compared to wt hippocampi, miR-155 ko hippocampi had a reduced inflammatory signature (e.g., decreased IL-6, TNF-a) and female miR-155 ko mice increased ciliary neurotrophic factor expression. Together, these data highlight the importance of studying microRNAs in the context of anxiety and depression and identify miR-155 as a novel potential therapeutic target for improving mood disorders.
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PMID:MicroRNA-155 deletion reduces anxiety- and depressive-like behaviors in mice. 2655 29


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