scholarly journals Immunotoxicity of 3 Chemical Forms of Beryllium Following Inhalation Exposure

2011 ◽  
Vol 30 (5) ◽  
pp. 538-545 ◽  
Author(s):  
Caroline Muller ◽  
Fariba Salehi ◽  
Bruce Mazer ◽  
Michèle Bouchard ◽  
Ariane Adam-Poupart ◽  
...  
Keyword(s):  
Fine Particles ◽  
Inhalation Exposure ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Chemical Forms ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor ◽  
Severe Lung

The toxicity of 3 chemical forms of beryllium (Be) was compared in this study. A total of 160 mice equally divided into 4 groups were exposed by inhalation (nose only) for 3 consecutive weeks, 5 d/week, 6 h/d. One group was used as control, while the 3 others were exposed to fine particles of Be metal, Be oxide (BeO), or Be aluminum (BeAl). Except for the controls, the target level of exposure was 250 μg/m3. In all, 35 mice/group were sacrificed 1 week postexposure and another 5 mice 3 weeks postexposure. The BeO group showed the highest lung Be concentration with higher interleukin 12 (IL-12) and interferon-γ (IFN-γ) levels, while the Be group produced the most severe lung inflammation and higher tumor necrosis factor-α (TNF-α) and CD4+ T cells levels. Data suggested that Be and BeO apparently produced more pulmonary toxicity than BeAl. However, this conclusion is not definitive, because of different confounding factors such as particle sizes, specific surface area, and solubility.

scholarly journals Intracellular Antimicrobial Activity in the Absence of Interferon-γ: Effect of Interleukin-12 in Experimental Visceral Leishmaniasis in Interferon-γ Gene-disrupted Mice

1997 ◽  
Vol 185 (7) ◽  
pp. 1231-1240 ◽  
Author(s):  
Alice P. Taylor ◽  
Henry W. Murray
Keyword(s):  
Antimicrobial Activity ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Gene Knockout ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Tnf Α ◽  
Ifn Γ ◽  
Independent Effects ◽  
Factor Α

Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-γ (IFN-γ) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. This late-developing IFN-γ–independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-α (TNF-α): L. donovani infection induced TNF-α mRNA expression in parasitized GKO livers and neutralization of TNF-α reversed control at week 12. 7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-γ–independent effects. The action of IL-12 against L. donovani was TNF-α dependent and required the activity of inducible nitric oxide synthase. These results point to the presence of an IFN-γ–independent antimicrobial mechanism, mediated by TNF-α, which remains quiescent until activated late in the course of experimental visceral leishmaniasis. However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.

Selective suppression of IL-12 production by human herpesvirus 6

Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2877-2884 ◽  
Author(s):  
Alison Smith ◽  
Fabio Santoro ◽  
Giulia Di Lullo ◽  
Lorenzo Dagna ◽  
Alessia Verani ◽  
...  
Keyword(s):  
Human Herpesvirus ◽  
Interferon Γ ◽  
Immunosuppressive Agent ◽  
Interleukin 12 ◽  
Human Herpesvirus 6 ◽  
Rnase Protection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Herpesvirus 6 ◽  
Factor Α

Abstract Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of HIV disease. Exposure of human macrophages to HHV-6A or HHV-6B profoundly impaired their ability to produce interleukin 12 (IL-12) upon stimulation with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). By contrast, the production of tumor necrosis factor–α (TNF-α); regulated on activation, normal T-cell expressed and secreted (RANTES); and macrophage inflammatory protein 1β (MIP-1β) was not negatively affected. To exclude the involvement of IL-12–suppressive cytokines, such as IL-10 and TNF-α, the viral stocks were fractionated by ultra-centrifugation. The bulk of the suppressive activity was recovered within the virion-rich pelleted fraction that was virtually devoid of such cytokines. IL-12 suppression was independent of viral replication, and the effect was not abrogated upon ultraviolet-light inactivation of the viral inoculum. The mechanism of HHV-6–mediated IL-12 suppression was investigated by RNase protection assays, which demonstrated unaltered levels of IL-12 p35 mRNA and only a modest reduction in p40 mRNA, which was insufficient to account for the near-complete loss of both extracellular and intracellular IL-12 protein. Moreover, both the IFN-γ and the LPS signaling pathways were intact in HHV-6–treated cells. These data suggest that HHV-6 can dramatically affect the generation of effective cellular immune responses, providing a novel potential mechanism of HHV-6–mediated immunosuppression.

Systemic Sclerosis Fibroblasts Show Specific Alterations of Interferon-γ and Tumor Necrosis Factor-α-induced Modulation of Interleukin 6 and Chemokine Ligand 2

2012 ◽  
Vol 39 (5) ◽  
pp. 979-985 ◽  
Author(s):  
ALESSANDRO ANTONELLI ◽  
POUPAK FALLAHI ◽  
SILVIA MARTINA FERRARI ◽  
DILIA GIUGGIOLI ◽  
MICHELE COLACI ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Tumor Necrosis Factor ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interferon Γ ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Objective.We evaluated the effect of interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) on the secretion of prototype proinflammatory cytokine interleukin 6 (IL-6), compared to T-helper 1 [Th1; chemokine (C-X-C motif) ligand 10 (CXCL10)] or Th2 [chemokine (C-C motif) ligand 2 (CCL2)] chemokines, in primary cultured fibroblasts from patients with systemic sclerosis (SSc) at an early stage of the disease.Methods.Fibroblast cultures from 5 SSc patients (disease duration < 2 yrs) and 5 healthy controls were evaluated for the production of IL-6, CXCL10, and CCL2 at the basal level and after stimulation with IFN-γ and/or TNF-α.Results.SSc fibroblasts basally produced higher levels of IL-6 than controls, while no difference was observed about CCL2 and CXCL10. TNF-α was able to dose-dependently induce IL-6 and CCL2 secretion in SSc, but not in control fibroblasts. By stimulation with increasing doses of IFN-γ, SSc fibroblasts were induced to secrete CCL2 and CXCL10, while no effect was observed on IL-6. The combination of IFN-γ and TNF-α induced a strong secretion of IL-6 and CCL2 in SSc fibroblasts but not in controls. In contrast, the synergistic effect of IFN-γ and TNF-α on CXCL10 secretion was similar in SSc fibroblasts and in controls.Conclusion.SSc fibroblasts participate in the self-perpetuation of inflammation by releasing IL-6, CXCL10, and CCL2 under the influence of IFN-γ and/or TNF-α. SSc fibroblasts are more active than controls in the secretion of IL-6 at baseline, and in the production of IL-6 and CCL2 under the combined IFN-γ/TNF-α stimulation.

scholarly journals Proinflammatory cytokines tumor necrosis factor-α and interferon-γ alter tight junction structure and function in the rat parotid gland Par-C10 cell line

2008 ◽  
Vol 295 (5) ◽  
pp. C1191-C1201 ◽  
Author(s):  
Olga J. Baker ◽  
Jean M. Camden ◽  
Robert S. Redman ◽  
Jonathan E. Jones ◽  
Cheikh I. Seye ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Interferon Γ ◽  
Anion Secretion ◽  
Cell Monolayers ◽  
Tnf Α ◽  
Rat Parotid Gland ◽  
Ifn Γ ◽  
Rat Parotid ◽  
Factor Α ◽  
Necrosis Factor

Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-α and IFN-γ decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current ( Isc) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y2 nucleotide receptor agonist. In contrast, TNF-α and IFN-γ had no effect on agonist-induced increases in the intracellular calcium concentration [Ca2+]i in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-α and IFN-γ increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-α, but not IFN-γ, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-γ causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.

Abstract 5551: Double Deficiency of Tumor Necrosis Factor-α and Interferon-γ in Bone Marrow-Derived Cells Prevents Neointimal Formation in a Murine Model of Vascular Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideki Murayama ◽  
Masafumi Takahashi ◽  
Yuji Shiba ◽  
Masaya Takamoto ◽  
Hirohiko Ise ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vascular Injury ◽  
Tumor Necrosis ◽  
Interferon Γ ◽  
Neointimal Formation ◽  
Tnf Α ◽  
Bone Marrow Derived Cells ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Neointimal formation after percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Recent evidence indicates that inflammatory responses induced by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are involved in the progression of neointimal formation. However, the role of TNF-α and IFN-γ in the restenosis after PCI has not been fully understood. The purpose of this study is to examine the impact of TNF-α and IFN-γ in bone marrow-derived cells in the development of neointimal formation after vascular injury in mice. Wild-type (WT), TNF-α-deficient (TNF-α −/− ), IFN-γ-deficient (IFN-γ −/− ), and TNF-α/IFN-γ double-deficient (DKO) mice were subjected to wire-mediated vascular injury of the right femoral artery. Immunohistochemical analysis showed the expression of TNF-α and IFN-γ was detected in the neointimal lesion of WT mice, but these cytokines were not detected in the lesion of the corresponding deficient mice. Neointimal formation was significantly reduced after the injury in the DKO mice, compared to that in the WT, TNF-α −/− , and IFN-γ −/− mice (I/M ratio, WT: 2.28±0.17, TNF-α −/− : 2.13±0.20, IFN-γ −/− : 2.37±0.16, DKO: 1.32±0.10, p<0.05, each n=14–17). No significant difference in reendothelialization (CD31 staining) was observed among these groups. Further, vascular smooth muscle cell (α-SMA) and macrophage (F4/80) contents in the neointimal area also did not differ among the groups. The number of proliferating cell nuclear antigen (PCNA) and Ki-67 positive cells in the neointimal lesion was significantly decreased in DKO mice. To determine the contribution of bone marrow cells, we developed 3 types of bone marrow chimeric (BMT Wild→Wild , BMT DKO→Wild , and BMT Wild→DKO ) mice. The neointimal formation in BMT DKO→Wild mice was significantly reduced as compared to that in BMT Wild→Wild (I/M ratio, p<0.05, each n=7) and BMT Wild→DKO mice (p<0.05). These results suggest that the lack of TNF-α and IFN-γ in bone marrow-derived cells synergistically prevents neointimal formation after vascular injury and provide new insights into the mechanisms underlying the restenosis after PCI.

"Tien-Hsien Liquid" Can Modulate Antigen-Stimulated Cytokine Production by T-Cells Isolated from Patients with Recurrent Aphthous Ulcerations

2005 ◽  
Vol 33 (04) ◽  
pp. 559-571 ◽  
Author(s):  
Andy Sun ◽  
Jean-San Chia ◽  
Won-Bo Wang ◽  
Chun-Pin Chiang
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Recurrent aphthous ulcerations (RAU) represent a common oral mucosal disease with altered humoral and cellular immunities. Tien-Hsien liquid (THL) is an extract of Chinese medicinal herbs with immunomodulating effects. Our previous study found that THL can modulate the antigen-stimulated proliferative response of peripheral blood mononuclear cells and T-cells isolated from RAU patients. In this study, we further tested whether THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. To achieve this goal, T-cells isolated from 19 RAU patients were incubated with phytohemagglutinin (PHA), glutaraldehyde-inactivated tetanus toxoid (TT), glucosyltransferase D (GtfD), or antigens of Streptococcus mutans in the presence or absence of THL. The levels of interleukin (IL)-2, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, or IL-10 in the supernatants of T-cell cultures were measured by cytokine enzyme-linked immunosorbent assay (ELISA) kits. We found that THL significantly increased the PHA- or TT-stimulated TNF-α, IL-6, and IL-10 production by T-cells isolated from RAU patients. However, THL could also significantly decrease the TT-stimulated IL-2 production, the GtfD-stimulated IL-2, TNF-α, IL-6 and IL-10 production, and the S. mutans-stimulated IFN-γ, TNF-α, and IL-10 production by T-cells isolated from RAU patients. These results indicate that THL can modulate the antigen-stimulated cytokine production by T-cells isolated from RAU patients. Because RAU is probably a Thl-mediated disease with elevated levels of IL-2, IFN-γ, TNF-α and IL-6 in either the patient's sera or oral lesions and these increased levels of cytokines can be reduced by THL, we suggest that THL may be a potential immunoceutical agent for treatment of RAU.

scholarly journals Tumour necrosis factor-α and interferon-γ synergistically activate the RANTES promoter through nuclear factor κB and interferon regulatory factor 1 (IRF-1) transcription factors

2000 ◽  
Vol 350 (1) ◽  
pp. 131-138 ◽  
Author(s):  
Ahn Hwee LEE ◽  
Jeong-Ho HONG ◽  
Yeon-Soo SEO
Keyword(s):  
Binding Sites ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Regulatory Factor ◽  
Cis Acting ◽  
Tnf Α ◽  
Ifn Γ ◽  
Rantes Promoter ◽  
Factor Α ◽  
Necrosis Factor

Inflammatory cytokines such as tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) synergistically activate expression of the RANTES (regulated upon activation, normal T-cell expressed and secreted) gene, which plays a crucial role in the chemoattraction of leukocytes during the inflammatory response. To understand at the molecular level the mechanism by which the two cytokines activate RANTES gene expression, we determined the requirement of cis-acting elements in the RANTES promoter and trans-acting factors. The murine RANTES promoter contained one putative interferon regulatory factor, IRF, and three putative nuclear factor κB (NF-κB) binding sites. Specific destruction of the IRF binding site and one of the three NF-κB binding sites abolished the inducibility of promoter activity by IFN-γ and TNF-α, respectively. In contrast, mutation of the other two putative NF-κB binding sites did not affect RANTES promoter activity significantly. In addition, the RANTES promoter was stimulated by co-transfection of plasmids that expressed either p65, an NF-κB family protein, or the IRF-1 transcription factor. RANTES promoters with mutations in the NF-κB or IRF binding sites were not stimulated by p65 or IRF-1 expression, respectively. In electrophoretic mobility-shift and immunologic assays, we showed that IRF-1 was induced after cells were treated with IFN-γ and that NF-κB was activated by TNF-α treatment. These results demonstrate that both NF-κB and IRF-1 transcription factors mediate the induction of RANTES expression via their cognate cis-acting elements when cells are stimulated by TNF-α and IFN-γ.

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