scholarly journals Modulation of Intracellular Growth ofListeria monocytogenesin Human Enterocyte Caco‐2 Cells by Interferon‐γ and Interleukin‐6: Role of Nitric Oxide and Cooperation with Antibiotics

1999 ◽  
Vol 180 (4) ◽  
pp. 1195-1204 ◽  
Author(s):  
Youssef Ouadrhiri ◽  
Yves Sibille ◽  
Paul M. Tulkens
Keyword(s):  
Nitric Oxide ◽  
Interleukin 6 ◽  
Interferon Γ ◽  
Intracellular Growth ◽  
Human Enterocyte

scholarly journals Uropathogenic Escherichia coli-Induced Inflammation Alters Mouse Urinary Bladder Contraction via an Interleukin-6-Activated Inducible Nitric Oxide Synthase-Related Pathway

2009 ◽  
Vol 77 (8) ◽  
pp. 3312-3319 ◽  
Author(s):  
Te I. Weng ◽  
Hsiao Yi Wu ◽  
Pei Ying Lin ◽  
Shing Hwa Liu
Keyword(s):  
Nitric Oxide ◽  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Urinary Bladder ◽  
Tract Infection ◽  
Interleukin 6 ◽  
Electrical Field Stimulation ◽  
E Coli

ABSTRACT Escherichia coli is the most common cause of urinary tract infection. Elevated blood and urine interleukin-6 (IL-6) levels have been shown in inflammatory urinary tract diseases. The role of IL-6 in mediating the urodynamic dysfunction in response to E. coli-induced urinary tract infection has not yet been fully elucidated. In this study, we investigated the role of IL-6 in the nitric oxide (NO)-triggered alteration of contractile responses in the urinary bladder under an E. coli-induced inflammatory condition. The electrical field stimulation (EFS)-evoked contractions of the isolated detrusor strips, and immunoblotting for detecting protein expression in the bladders was measured short term (1 h) or long term (6 or 24 h) after intraperitoneal injection of E. coli endotoxin (lipopolysaccharide [LPS]) or intravesical instillation of human pyelonephritogenic E. coli-J96 (O4:K6) strain or LPS into mice. IL-6 and NO productions were increased in the urinary bladders of mice 1 to 24 h after LPS or E. coli-J96 treatment. Inducible NO synthase (iNOS) expression and protein kinase C (PKC) activation and EFS-evoked detrusor contractions were increased in the bladders at 6 h after LPS or E. coli-J96 treatment, which could be reversed by anti-IL-6 antibody and iNOS inhibitor aminoguanidine. At 1 h after LPS administration, bladder NO generation, endothelial NOS expression, and EFS-evoked detrusor contractions were effectively increased, whereas anti-IL-6 antibody could not reverse these LPS-induced responses. These results indicate that IL-6 may play an important role in the iNOS/NO-triggered PKC-activated contractile response in urinary bladder during E. coli or LPS-induced inflammation.

scholarly journals Suppression of LPS-induced Interferon-γ and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4591-4597 ◽  
Author(s):  
Rujuan Dai ◽  
Rebecca A. Phillips ◽  
Yan Zhang ◽  
Deena Khan ◽  
Oswald Crasta ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Immune Modulation ◽  
Interferon Γ ◽  
Negative Regulator ◽  
Pcr Analysis ◽  
Innate Immune Responses ◽  
Splenic Lymphocytes ◽  
Aberrant Expression ◽  
Oxide Synthase

Abstract MicroRNAs (miRNAs), recently identified noncoding small RNAs, are emerging as key regulators in homeostasis of the immune system. Therefore, aberrant expression of miRNAs may be linked to immune dysfunction, such as in chronic inflammation and autoimmunity. In this study, we investigated the potential role of miRNAs in estrogen-mediated regulation of innate immune responses, as indicated by up-regulation of lipopolysaccharide (LPS)–induced interferon-gamma (IFNγ), inducible nitric oxide synthase (iNOS), and nitric oxide in splenic lymphocytes from estrogen-treated mice. We found that miR-146a, a negative regulator of Toll-like receptor (TLR) signaling, was decreased in freshly isolated splenic lymphocytes from estrogen-treated mice compared with placebo controls. Increasing the activity of miR-146a significantly inhibited LPS-induced IFNγ and iNOS expression in mouse splenic lymphocytes. Further, miRNA microarray and real-time reverse transcriptase–polymerase chain reaction (RT-PCR) analysis revealed that estrogen selectively up-regulates/down-regulates the expression of miRNAs in mouse splenic lymphocytes. miR-223, which is markedly enhanced by estrogen, regulates LPS-induced IFNγ, but not iNOS or nitric oxide in splenic lymphocytes. Inhibition of miR-223 activity decreased LPS-induced IFNγ in splenic lymphocytes from estrogen-treated mice. Our data are the first to demonstrate the selective regulation of miRNA expression in immune cells by estrogen and are indicative of an important role of miRNAs in estrogen-mediated immune regulation.

scholarly journals Oxygen tension limits nitric oxide synthesis by activated macrophages

2000 ◽  
Vol 350 (3) ◽  
pp. 709-716 ◽  
Author(s):  
Charles C. MCCORMICK ◽  
Wai Ping LI ◽  
Monica CALERO
Keyword(s):  
Nitric Oxide ◽  
Oxygen Tension ◽  
Interferon Γ ◽  
Activated Macrophages ◽  
Calcium Dependent ◽  
Oxide Synthase ◽  
Nos Gene ◽  
High Output

Previous studies have established that constitutive calcium-dependent (‘low-output’) nitric oxide synthase (NOS) is regulated by oxygen tension. We have investigated the role of oxygen tension in the synthesis of NO by the ‘high-output’ calcium-independent NOS in activated macrophages. Hypoxia increased macrophage NOS gene expression in the presence of one additional activator, such as lipopolysaccharide or interferon-γ, but not in the presence of both. Hypoxia markedly reduced the synthesis of NO by activated macrophages (as measured by accumulation of nitrite and citrulline), such that, at 1% oxygen tension, NO accumulation was reduced by 80–90%. The apparent Km for oxygen calculated from cells exposed to a range of oxygen tensions was found to be 10.8%, or 137µM, O2 This value is considerably higher than the oxygen tension in tissues, and is virtually identical to that reported recently for purified recombinant macrophage NOS. The decrease in NO synthesis did not appear to be due to diminished arginine or cofactor availability, since arginine transport and NO synthesis during recovery in normoxia were normal. Analysis of NO synthesis during hypoxia as a function of extracellular arginine indicated that an altered Vmax, but not KmArg, accounted for the observed decrease in NO synthesis. We conclude that oxygen tension regulates the synthesis of NO in macrophages by a mechanism similar to that described previously for the calcium-dependent low-output NOS. Our data suggest that oxygen tension may be an important physiological regulator of macrophage NO synthesis in vivo.

Role of Interferon- γ and Nitric Oxide in Pulmonary Edema and Death Induced by Lipopolysaccharide

2000 ◽  
Vol 161 (1) ◽  
pp. 110-117 ◽  
Author(s):  
HUBERTINE HEREMANS ◽  
CHRISTIANE DILLEN ◽  
MARLEEN GROENEN ◽  
PATRICK MATTHYS ◽  
ALFONS BILLIAU
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Edema ◽  
Interferon Γ

scholarly journals Role of vav1 in the Lipopolysaccharide-Mediated Upregulation of Inducible Nitric Oxide Synthase Production and Nuclear Factor for Interleukin-6 Expression Activity in Murine Macrophages

2004 ◽  
Vol 11 (3) ◽  
pp. 525-531 ◽  
Author(s):  
Sandip A. Godambe ◽  
Katherine M. Knapp ◽  
Elizabeth A. Meals ◽  
B. Keith English
Keyword(s):  
Nitric Oxide ◽  
Inducible Nitric Oxide Synthase ◽  
Interleukin 6 ◽  
Macrophage Activation ◽  
Protein Accumulation ◽  
Nuclear Factor ◽  
Oxide Synthase ◽  
Mutant Forms ◽  
Inducible Nitric Oxide

ABSTRACT vav1 has been shown to play a key role in lymphocyte development and activation, but its potential importance in macrophage activation has received little attention. We have previously reported that exposure of macrophages to bacterial lipopolysaccharide (LPS) leads to increased activity of hck and other src-related tyrosine kinases and to the prompt phosphorylation of vav1 on tyrosine. In this study, we tested the role of vav1 in macrophage responses to LPS, focusing on the upregulation of nuclear factor for interleukin-6 expression (NF-IL-6) activity and inducible nitric oxide synthase (iNOS) protein accumulation in RAW-TT10 murine macrophages. We established a series of stable cell lines expressing three mutant forms of vav1 in a tetracycline-regulatable fashion: (i) a form producing a truncated protein, vavC; (ii) a form containing a point mutation in the regulatory tyrosine residue, vavYF174; and (iii) a form with an in-frame deletion of 6 amino acids required for the guanidine nucleotide exchange factor (GEF) activity of vav1 for rac family GTPases, vavGEFmt. Expression of the truncated mutant (but not the other two mutants) has been reported to interfere with T-cell activation. In contrast, we now demonstrate that expression of any of the three mutant forms of vav1 in RAW-TT10 cells consistently inhibited LPS-mediated increases in iNOS protein accumulation and NF-IL-6 activity. These data provide direct evidence for a role for vav1 in LPS-mediated macrophage activation and iNOS production and suggest that vav1 functions in part via activation of NF-IL-6. Furthermore, these findings indicate that the GEF activity of vav1 is required for its ability to mediate macrophage activation by LPS.

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