Increased expression of the interleukin-10 gene by alveolar macrophages in interstitial lung disease

1997 ◽  
Vol 273 (3) ◽  
pp. L676-L683 ◽  
Author(s):  
J. A. Martinez ◽  
T. E. King ◽  
K. Brown ◽  
C. A. Jennings ◽  
L. Borish ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Alveolar Macrophages ◽  
Interleukin 10 ◽  
Interstitial Lung Diseases ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans with organizing pneumonia (BOOP) are interstitial lung diseases of unknown pathogenesis. Alveolar macrophages play a major role in the regulation of the inflammatory response in these diseases through their ability to produce cytokines that modify the inflammatory response. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) exhibit proinflammatory and anti-inflammatory actions, respectively, and thus an imbalance in the expression of these cytokines may contribute to the pathogenesis of IPF and BOOP. Therefore, we quantified IL-10 and TNF-alpha mRNA levels in alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with IPF and BOOP and in normal healthy volunteers. The level of TNF-alpha mRNA in macrophages obtained from IPF and BOOP patients was not significantly different from normal healthy subjects. However, macrophages from patients with IPF and BOOP expressed increased levels of IL-10 mRNA compared with healthy controls. In addition, stimulation of alveolar macrophages with lipopolysaccharide in the presence of a neutralizing anti-IL-10 antibody augmented the production of TNF-alpha over that seen in the absence of anti-IL-10 antibody, suggesting that the increased expression of IL-10 by alveolar macrophages may act to control the expression of TNF-alpha. Paradoxically, measurement of IL-10 protein in cell-free BAL fluid revealed lower amounts of the protein in patients with IPF and BOOP compared with healthy controls.

scholarly journals Local and systemic influence of toxic levels of airborne ozone on the inflammatory response in rats

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Małgorzata Chmielewska-Krzesińska ◽  
Krzysztof Wąsowicz
Keyword(s):  
Inflammatory Response ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Interleukin 10 ◽  
Necrosis Factor Alpha ◽  
Genes Expression ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Necrosis Factor

Abstract Introduction Ozone is not harmful itself; however, it directly oxidises biomolecules and produces radical-dependent cytotoxicity. Exposure to ozone is by inhalation and therefore the lungs develop the main anti-inflammatory response, while ozone has an indirect impact on the other organs. This study investigated the local and systemic effects of the ozone-associated inflammatory response. Material and Methods Three groups each of 5 Wistar Han rats aged 6 months were exposed for 2h to airborne ozone at 0.5 ppm and a fourth identical group were unexposed controls. Sacrifice was at 3h after exposure for control rats and one experimental group and at 24 h and 48 h for the others. Lung and liver samples were evaluated for changes in expression of transforming growth factor beta 1, anti-inflammatory interleukin 10, pro-inflammatory tumour necrosis factor alpha and interleukin 1 beta and two nuclear factor kappa-light-chain-enhancer of B cells subunit genes. Total RNA was isolated from the samples in spin columns and cDNA was synthesised in an RT-PCR. Expression levels were compared to those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and analysed statistically. Results All variables changed non-linearly over time comparing experimental groups to the control. Conspicuous expression changes in the subunit genes and cytokines were observed in both evaluated organs. Conclusion Locally and systemically, inflammation responses to ozone inhalation include regulation of certain genes’ expression. The mechanisms are unalike in lungs and liver but ozone exerts a similar effect in both organs. A broader range of variables influential on ozone response should be studied in the future.

Colchicine has opposite effects on interleukin-1 beta and tumor necrosis factor-alpha production

1991 ◽  
Vol 261 (4) ◽  
pp. L315-L321 ◽  
Author(s):  
J. N. Allen ◽  
D. J. Herzyk ◽  
M. D. Wewers
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cytokine Production ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Interleukin 1 Beta ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

To study the role of microtubules in cytokine production, the effect of the microtubule depolymerizing agent colchicine on lipopolysaccharide endotoxin (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) release by blood monocytes and alveolar macrophages were examined. Immunofluorescence microscopy demonstrated that LPS resulted in the appearance of microtubule-containing cytoplasmic appendages and that colchicine, which resulted in microtubule disruption in monocytes, blocked appendage formation. Colchicine resulted in approximately 50% increase in LPS-induced IL-1 beta release and a 50% decrease in LPS-induced TNF-alpha release by human monocytes at all doses of LPS tested. Although colchicine resulted in a statistically significant increase in LPS-stimulated human alveolar macrophage IL-1 beta release, the increase was not as great as that observed with monocytes. Northern blot analysis suggested that the colchicine effect occurs pretranslationally because colchicine caused an increase in LPS-stimulated IL-1 beta mRNA levels and a decrease in TNF-alpha mRNA levels. These results suggest that microtubules contribute to the regulation of endotoxin-stimulated mononuclear phagocyte cytokine production and that this regulation differs significantly between IL-1 beta and TNF-alpha.

scholarly journals Differential expression of adrenomedullin and resistin in 3T3-L1 adipocytes treated with tumor necrosis factor-alpha

2003 ◽  
pp. 231-238 ◽  
Author(s):  
Y Li ◽  
K Totsune ◽  
K Takeda ◽  
K Furuyama ◽  
S Shibahara ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Resistin Mrna

DESIGN: It has recently been shown that deficiency of adrenomedullin (AM), a potent vasodilator peptide, leads to insulin resistance. We studied expression of AM in NIH 3T3-L1 adipocytes and compared it with expression of resistin, an adipocyte-derived peptide hormone that is proposed to cause insulin resistance. Moreover, we studied the effects of tumor necrosis factor-alpha (TNF-alpha), a known mediator of insulin resistance, on the expression of AM and resistin in 3T3-L1 adipocytes. METHODS: 3T3-L1 cells were induced to differentiate to adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine. Expression of AM mRNA and resistin mRNA was examined by Northern blot analysis. Immunoreactive AM in the medium was measured by RIA. RESULTS: AM mRNA was expressed in preadipocytes, but barely detectable in adipocytes. Immunoreactive AM was detected in the medium of both preadipocytes and adipocytes, with about 2.5 times higher levels found in preadipocytes. In contrast, resistin mRNA was expressed in adipocytes, whereas it was not detected in preadipocytes. Treatment with TNF-alpha increased AM expression in both adipocytes and preadipocytes, whereas it decreased resistin mRNA levels in adipocytes. CONCLUSIONS: The present study has shown that AM expression was down-regulated and resistin expression was up-regulated during adipocyte differentiation of 3T3-L1 cells. TNF-alpha acted as a potent negative regulator of resistin expression and a potent positive regulator of AM expression in adipocytes, raising the possibility that in addition to its known actions in causing insulin resistance, TNF-alpha may also have actions against insulin resistance through AM and resistin.

scholarly journals Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes.

1996 ◽  
Vol 184 (1) ◽  
pp. 51-60 ◽  
Author(s):  
P Brandtzaeg ◽  
L Osnes ◽  
R Ovstebø ◽  
G B Joø ◽  
A B Westvik ◽  
...  
Keyword(s):  
Septic Shock ◽  
Interleukin 10 ◽  
Tnf Alpha ◽  
Functional Assay ◽  
Human Monocytes ◽  
Necrosis Factor Alpha ◽  
Inhibitory Capacity ◽  
Activation Products ◽  
Factor Alpha ◽  
Necrosis Factor

We have developed a functional assay to study the inflammatory capacity of plasma collected from patients with severe gram-negative septic shock. In this assay, elutriation-purified, cryo-preserved human monocytes from one healthy donor are combined with plasma from patients with severe persistent septic shock for 5 h. Subsequently, the plasma is removed, medium added, and procoagulant activity (PCA) and secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) measured after 18-h incubation. Plasma from 10 patients (6 died) infected with Neisseria meningitidis previously shown to contain high levels of native lipopolysaccharide (LPS) (median 2,700 pg/ml), TNF-alpha, IL-6, IL-8, and complement activation products, had a low net spontaneous inflammatory capacity on the monocytes. The median levels of PCA, TNF-alpha, and IL-6 were 5, 0, and 4%, respectively, of the monocyte activities induced by normal plasma boosted with purified N. meningitidis (Nm)-LPS (2,500 pg/ml; net LPS-boosted capacity, 100%). The levels of PCA, TNF-alpha, and IL-6 obtained with plasma from shock patients were not different from those induced by plasma from 10 meningococcal patients without shock or with plasma from healthy persons. Boosting shock plasma with 2,500 pg/ml Nm-LPS had little effect on the monocyte activities since the median values of PCA, TNF-alpha, and IL-6 revealed a minimal increase from 5, 0, and 4% to 9, 2, and 6%, respectively. The shock plasmas revealed a strong LPS-inhibitory capacity that was largely absent in plasmas from 10 meningococcal patients without shock since the median levels of PCA, TNF-alpha, and IL-6 increased from 5, 0, and 0% to 135, 51, and 73%, respectively, after boosting with 2,500 pg/ml Nm-LPS. The LPS-inhibitory capacity was closely associated with the levels of IL-10. The median levels of IL-10 were 19,000 pg/ml in nine shock patients vs. 22 pg/ml in nine nonshock patients with systemic meningococcal disease. Removal of native IL-10 by immunoprecipitation restored the capacity of plasmas to induce monocyte activation either by native LPS or by boosting with Nm-LPS. IL-4 and TGF-beta were not detected in shock plasmas. In 24 patients with detectable meningococcal LPS ( > 10 pg/ml, 0.1 endotoxin units/ml), the levels of IL-10 were correlated to the levels of LPS (r = 0.79, P < 0.001). IL-10 declined from initiation of antibiotic therapy and paralleled the levels of native LPS. Decreasing levels of IL-10 in serially collected shock plasmas were directly related to increasing monocyte responsiveness after Nm-LPS boosting. These results suggest that IL-10 plays a major role in containing activation of monocytes and possibly other LPS-responsive cells during overwhelming meningococcemia.

scholarly journals Recombinant human tumor necrosis factor alpha regulates c-myc expression in HL-60 cells at the level of transcription

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 200-205
Author(s):  
A Tobler ◽  
D Johnston ◽  
HP Koeffler
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Human Tumor ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Human Tumor Necrosis Factor ◽  
Mrna Accumulation ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Recombinant human tumor necrosis factor alpha (TNF alpha) effectively inhibits clonal growth of leukemic cells from patients and several cell lines, including the promyelocytic HL-60 cells. Decreased expression of the c-myc oncogene is linked to growth arrest and terminal cellular differentiation. The present study characterizes the effect of TNF alpha on the regulation of the c-myc gene in HL-60 cells. TNF alpha (100 U/mL) rapidly inhibited messenger RNA (mRNA) accumulation of c-myc with a 50% reduction in less than one hour. Dose-response studies showed that a 50% reduction of c-myc mRNA occurred in the range of 15 U/mL. In vitro nuclear run-on experiments showed that this decrease of c-myc-mRNA accumulation was the result of a reduced rate of transcription of c-myc by TNF alpha. Further studies demonstrated that TNF alpha did not post-transcriptionally alter levels of c-myc mRNA, and the inhibitory action of TNF alpha on c-myc expression in HL-60 cells did not depend on new protein synthesis. In the conditions of all the experiments, TNF alpha did not affect cell viability. By contrast, TNF alpha (500 U/mL) did not decrease mRNA levels of c-myc in an HL-60 variant cell line whose growth was not inhibited by TNF alpha; also TNF alpha (500 U/mL) increased c-myc-mRNA levels in normal fibroblasts whose growth is known to be stimulated by TNF alpha. These findings, in concert with prior studies, show a close association between growth inhibition of HL-60 cells and decreased levels of mRNA coding for c-myc.

Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung

1996 ◽  
Vol 270 (5) ◽  
pp. L714-L721 ◽  
Author(s):  
G. S. Pryhuber ◽  
C. Bachurski ◽  
R. Hirsch ◽  
A. Bacon ◽  
J. A. Whitsett
Keyword(s):  
Gene Expression ◽  
Lung Inflammation ◽  
Intraperitoneal Administration ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Acute Lung Inflammation ◽  
Antibody Treatment ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Respiratory failure secondary to acute lung inflammation is associated with quantitative and qualitative abnormalities of pulmonary surfactant. The surfactant-associated proteins (SP)-A, -B, and -C are critical for normal surfactant function, synthesis, and metabolism.Tumor necrosis factor-alpha (TNF-alpha), a primary mediator of acute lung inflammation, decreased SP gene expression in vitro (32, 34). In the present in vivo study, transient T cell activation and TNF-alpha release were initiated by intraperitoneal administration of anti-CD3 antibody 145-2C11. Serum TNF-alpha was elevated 2 h after injection of the antibody. SP-B and -C mRNA were decreased 12 and 24 h after antibody treatment. Intratracheal murine TNF-alpha also resulted in decreased SP-B and SP-C mRNA levels in the bronchiolar and alveolar epithelium of adult FVB/N mice, as demonstrated by S1 nuclease protection and in situ hybridization assays, despite minimal histological inflammation. SP-A mRNA was not significantly altered after anti-CD3 antibody and was only mildly decreased after TNF-alpha. As previously reported, intercellular adhesion molecule-1 mRNA was elevated after intratracheal TNF-alpha. SP insufficiency contributes to the pathogenesis of pulmonary diseases associated with increased TNF-alpha, such as adult respiratory distress syndrome and pneumonia (8). TNF-alpha-mediated decrease in SP gene expression may contribute to the surfactant dysfunction and atelectasis observed in inflammatory lung diseases.

scholarly journals Interleukin 10 protects mice from lethal endotoxemia.

1993 ◽  
Vol 177 (4) ◽  
pp. 1205-1208 ◽  
Author(s):  
M Howard ◽  
T Muchamuel ◽  
S Andrade ◽  
S Menon
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Single Injection ◽  
Interleukin 10 ◽  
Tnf Alpha ◽  
Bacterial Sepsis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Interleukin 10 (IL-10) decreases production of IL-1, IL-6, and tumor necrosis factor alpha (TNF-alpha) in vitro, and neutralization of IL-10 in mice leads to elevation of the same monokines. We test here whether this monokine-suppressing property of IL-10 confers on it the capacity to protect mice from lipopolysaccharide-induced shock, a monokine-mediated inflammatory reaction. A single injection of 0.5-1 microgram of recombinant murine IL-10 reproducibly protected BALB/c mice from a lethal intraperitoneal injection of endotoxin. This result was obtained whether the IL-10 was administered concurrently with, or 30 min after the injection of endotoxin. The protective effect of IL-10 was reversed by prior injection of neutralizing anti-IL-10 antibodies, and correlated with a substantial decrease in endotoxin-induced TNF-alpha release. These data implicate IL-10 as a candidate for treatment of bacterial sepsis, and more generally as an effective antiinflammatory reagent.

scholarly journals Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors.

1991 ◽  
Vol 174 (1) ◽  
pp. 281-284 ◽  
Author(s):  
E Vannier ◽  
L C Miller ◽  
C A Dinarello
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
H2 Receptor ◽  
Factor Alpha ◽  
Necrosis Factor

Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after mast cell degranulation. Histamine (10(-5) M) markedly suppressed LPS-induced synthesis of TNF-alpha in both unfractionated PBMC (83% inhibition, p less than 0.001) and monocytes purified by positive selection of LeuM3+ cells (62% inhibition, p less than 0.05). The suppressive effect of histamine on TNF-alpha synthesis did not require the presence of T cells. The histamine-mediated decrease in TNF-alpha synthesis was not affected by indomethacin, nor by diphenhydramine, an H1 receptor antagonist, but was reversed by cimetidine or ranitidine, H2 receptor antagonists, in a dose-dependent manner. Suppression of TNF-alpha synthesis by histamine is likely to be a transcriptional event, since histamine (10(-5) M) reduced TNF-alpha mRNA levels fourfold. These results suggest that histamine release from mast cells may paradoxically limit the extent of inflammatory and immune reactions by suppressing local cytokine synthesis in H2 receptor-bearing cells.

scholarly journals POS0940 THE IMPACT OF TUMOUR NECROSIS FACTOR-ALPHA INHIBITOR TREATMENT ON WNT SIGNALING INHIBITORS, NOGGIN AND CYTOKINE LEVELS IN AXIAL SPONDYLOARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 733.1-733
Author(s):  
N. Atas ◽  
B. Çakir ◽  
F. Bakir ◽  
M. Uçar ◽  
H. Satiş ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Tnf Alpha ◽  
Healthy Controls ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
The Impact ◽  
Dickkopf 1 ◽  
Necrosis Factor

Background:Axial spondyloarthritis (axSpA) is a common chronic inflammatory disease of the axial skeleton. Some cytokines have important roles in initiation and progression of disease and are elevated in active disease. Additionally, Wnt signaling pathway inhibitors and noggin also appear to be involved in pathogenesis of ankylosing spondylitis. Anti-tumor necrosis factor-alpha (TNF) agents have dramatically improved the clinical outcome of axSpa; however, acceptable clinical improvement is not achieved in all patients and capacity of anti-TNF to slow or prevent structural damage still remains controversial.Objectives:To evaluate the effect of anti-TNF on inflammatory and noninflammatory milieu in patients with axSpA.Methods:In this prospective study we included 30 biologic treatment naive adult patients with axSpA and 30 healthy controls. All patients with high disease activity were treated with anti-TNF therapy for 6 months. Laboratory and clinical evaluation of all patients were performed at baseline and after 6 months of anti-TNF treatment. Following cytokines and wnt/BMP antagonists were measured; TNF-Alpha, COX-2, IL-6, IL-17, IL-22, IL-23, IL-33, dickkopf-1, sclerostin, noggin.Results:The mean age of patients with axSpA and healthy controls were 38.1±13.3 and 37.7±7.7 years, respectively (p>0.005). At baseline, the median (IQR) TNF-alpha was higher in axSpA patients when compared to healthy controls, 34.4 pg/ml (31.4-37.03) vs 18.1 pg/ml (12.1-28.4), (p<0.001), while the median (IQR) dickkopf-1 and sclerostin were lower in axSpA patients, 446.7 pg/ml (356.9-529.3) vs 1088.7 pg/ml (951.7-1244.4), (p<0.001) and 312.4 pg/ml (140.8-412.7) vs 412.3 pg/ml (295.4-512.8), (p<0.001), respectively. IL-17, IL-22, IL-33, dickkopf-1 and sclerostin increased with anti-TNF treatment (table 1).Conclusion:Elevation of some cytokines which are important in pathogenesis of axSpA and nonincrease in noggin with anti-TNF drugs may affect effectiveness of anti-TNF treatment.Table 1.Changes of cytokines, dickkopf-1, sclerostin and noggin with anti-TNF treatment.Pre-Anti-TNFPost-Anti-TNFP valueIL-645(39.1-68.8)47.6(27.3-61.1)0.750IL-1793.3 (85.1-104.8)102.1(86.6-114.6)0.026IL-22159,2 (151,9-178.4)183.5(156.3-304.6)0.033IL-2336.5 (26.1-52.9)41.3(28.4-55.5)0.658IL-33127.8 (106.6-186.1)147.06(128.5-213.4)0.016COX20.176 (0-0.374)0.202(0.051-1.151)0.469TNFalpha34.4(31.4-37.03)30.7(12.8-35.6)0.004Dickkopf-1446.7(356.9-529.3)881.3(663.1-972.2)<0.001Sclerostin312.4 (140.8-412.7)405.1(276.3-452.5)0.018Noggin48.3(17.04-153.9)31.2(11.3-103.7)0.264Disclosure of Interests:None declared

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