scholarly journals Interleukin-13 inhibits inducible nitric oxide synthase expression in human mesangial cells

1996 ◽  
Vol 313 (2) ◽  
pp. 641-646 ◽  
Author(s):  
Marta SAURA ◽  
Rosa MARTÍNEZ-DALMAU ◽  
Adrian MINTY ◽  
Dolores PÉREZ-SALA ◽  
Santiago LAMAS
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mesangial Cells ◽  
Inhibitory Effect ◽  
Northern Analysis ◽  
Inos Mrna ◽  
Dependent Manner ◽  
Human Mesangial Cells ◽  
Oxide Synthase ◽  
Stimulation Of

The synthesis of nitric oxide in inflammatory situations requires the expression of an inducible isoform of nitric oxide synthase (iNOS). Human mesangial cells (HMC) express an iNOS enzyme after exposure to multiple co-stimuli. In this study we have observed that while tumour necrosis factor-α, interleukin (IL)-1β, interferon-γ and bacterial lipopolysaccharide (LPS) were unable to significantly induce NO synthesis when used alone, they induced an evident stimulation of NO synthesis when used in various combinations. A mixture of the three cytokines (CM) and LPS resulted in a 10-15-fold stimulation of NO synthesis over control values which started to be significant after 16 h. The addition of IL-13, a cytokine with anti-inflammatory properties, inhibited CM/LPS-induced NO synthesis in a concentration-dependent manner. A marked inhibitory effect (60-65%) could be observed when HMC were treated with IL-13 (10 ng/ml) 24 h before, at the same time as, or even 4 h after the addition of CM/LPS. This inhibitory effect was still significant (25%) when IL-13 was added 16 h after CM/LPS. Northern analysis showed that IL-13-mediated iNOS inhibition was closely correlated with the suppression of iNOS mRNA expression. These results identify IL-13 as a powerful regulatory tool for the inhibition of NO synthesis in human cells, a property which may be pathophysiologically relevant in NO-related inflammatory processes.

scholarly journals Dexamethasone differentially affects interleukin 1β- and cyclic AMP-induced nitric oxide synthase mRNA expression in renal mesangial cells

1994 ◽  
Vol 304 (2) ◽  
pp. 337-340 ◽  
Author(s):  
D Kunz ◽  
G Walker ◽  
J Pfeilschifter
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cyclic Amp ◽  
Mesangial Cells ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Camp Analogue ◽  
Oxide Synthase ◽  
Inos Induction

Inducible nitric oxide synthase (iNOS) is expressed in renal mesangial cells in response to two principal classes of activating signals that interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin (IL)-1 beta or tumour necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP). We examined whether dexamethasone differentially affects iNOS induction in response to IL-1 beta and a membrane-permeable cAMP analogue, N6,O-2′-dibutyryladenosine 3′,5′-phosphate (Bt2cAMP). Nanomolar concentrations of dexamethasone suppress IL-1 beta- as well as Bt2cAMP-induced iNOS protein expression and production of nitrite, the stable end product of nitric oxide (NO) formation. In contrast, dexamethasone prevents induction of iNOS mRNA in response to Bt2cAMP without affecting IL-1 beta-triggered increase in iNOS mRNA levels. These data suggest that dexamethasone acts at different levels, depending on the stimulus used to suppress iNOS induction in mesangial cells.

Hydrogen peroxide downregulates IL-1-driven mesangial iNOS activity: implications for glomerulonephritis

1997 ◽  
Vol 272 (6) ◽  
pp. F721-F728 ◽  
Author(s):  
E. A. Jaimes ◽  
K. A. Nath ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Inos Mrna ◽  
No Production ◽  
Glomerular Injury ◽  
Inos Activity ◽  
Oxide Synthase

In glomerulonephritides, autacoids such as nitric oxide (NO), reactive oxygen species, and prostanoids are produced in increased amounts in response to cytokines such as interleukin-1 (IL-1). These autacoids influence the expression of glomerular injury by their direct as well as interactive actions. We studied the effect of hydrogen peroxide (H2O2) on NO production in rat mesangial cells. We demonstrate that transient exposure of mesangial cells to H2O2 prior to sustained exposure to IL-1 decreased extracellular accumulation of NO2/NO3 and cellular guanosine 3,'5'-cyclic monophosphate (cGMP) content. H2O2 markedly impaired inducible nitric oxide synthase (iNOS) activity induced by IL-1 directly measured by the conversion of L-[14C]arginine to L-[14C]citrulline. Such impairment in iNOS activity was accompanied by a parallel reduction in iNOS protein abundance but not by a reduced expression of iNOS mRNA. The inhibitory effect of H2O2 on NOS activity was further supported by peroxide-induced impairment in IL-1-driven, NO-dependent synthesis of prostaglandin E2. Our studies thus provide the first direct evidence of a posttranscriptional inhibitory effect of H2O2 on iNOS activity. Additionally, our studies uncover the existence of a previously unrecognized effect of H2O2 on the production of NO that may exert influence on the severity of glomerular injury during glomerular inflammation.

scholarly journals Effects of nitric oxide synthase inhibition on goat oocyte meiotic maturation

2013 ◽  
Vol 56 (1) ◽  
pp. 255-263
Author(s):  
M. H. Amale ◽  
A. Z. Shahneh ◽  
S. Nasrollahi
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inhibitory Effect ◽  
Nitric Oxide Donor ◽  
Meiotic Maturation ◽  
Dependent Manner ◽  
Cumulus Expansion ◽  
Maturation Medium ◽  
First Polar Body ◽  
Oxide Synthase

Abstract. Nitric oxide is a biological signalling molecule that plays a crucial role in oocyte maturation of mammalians. It is generated by the nitric oxide synthase enzyme from L-arginine. In this study we assessed the effect of nitric oxide synthase inhibition by Nω-nitro-L-arginine methyl ester (L-NAME) on meiotic maturation of goat oocytes. So, different concentrations of L-NAME (0.1, 1, 10 mM) were added to the maturation medium to evaluate the effect of inhibiting nitric oxide synthase on cumulus expansion and meiotic resumption of goat oocytes. The results showed that none of the concentrations affected cumulus expansion but the formation of the first polar body of the oocytes was suppressed in a dose dependent manner. The highest inhibitory effect was observed with 10 mM L-NAME. Moreover, to confirm the results and to evaluate whether this effect is reversible, 0.1 mM sodium nitroprusside (a nitric oxide donor) was added only to the maturation medium which had the highest concentration of L-NAME (10 mM). The concomitant addition of nitric oxide synthase inhibitor with nitric oxide donor reversed the inhibitory effect of L-NAME on meiotic maturation. These results indicated that the nitric oxide / nitric oxide synthase system is involved in the maturation of goat oocytes and that nitric oxide requirement for nuclear maturation is higher than that for cumulus expansion.

scholarly journals Molecular cloning and characterization of Ca2+-dependent inducible nitric oxide synthase from guinea-pig lung

1998 ◽  
Vol 333 (3) ◽  
pp. 795-799 ◽  
Author(s):  
Manabu SHIRATO ◽  
Tohru SAKAMOTO ◽  
Yoshiyuki UCHIDA ◽  
Akihiro NOMURA ◽  
Yukio ISHII ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Amino Acid ◽  
Nitric Oxide Synthase ◽  
Guinea Pig ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Mrna ◽  
Dependent Manner ◽  
Calmodulin Antagonist ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

We have isolated a full-length cDNA for an inducible nitric oxide synthase (iNOS) from guinea-pig lung. The cDNA has a 3447 bp open reading frame encoding 1149 amino acid residues. The deduced amino acid sequence is approx. 80% identical with iNOS of human epithelial cells and murine macrophages. Consensus recognition sites for cofactors are highly conserved. COS cell lysate transfected with the guinea-pig iNOS shows significant levels of nitric oxide synthase (NOS) activity, and this is inhibited by 79% by chelation of Ca2+ ions. The NOS activity is restored in a concentration-dependent manner by increasing the free Ca2+ level. The NOS activity is also inhibited by trifluoperazine, a calmodulin antagonist, which suggests that the Ca2+ dependence is due to Ca2+-dependent calmodulin binding to the enzyme. Northern blot analysis reveals that the cloned iNOS mRNA is expressed in the lung and the colon in normal guinea pigs. Stimulation in vivo by lipopolysaccharide induces the expression of iNOS in the kidney, the spleen and the colon, but in the lung the same stimulation decreases its expression. These results suggest that the cloned guinea-pig iNOS is distinct in characteristics and expression from previously described iNOS forms.

Cerebellar stimulation reduces inducible nitric oxide synthase expression and protects brain from ischemia

1998 ◽  
Vol 274 (6) ◽  
pp. H2035-H2045 ◽  
Author(s):  
Elena Galea ◽  
Eugene V. Golanov ◽  
Douglas L. Feinstein ◽  
Keith A. Kobylarz ◽  
Sara B. Glickstein ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Mrna ◽  
Cerebral Microvessels ◽  
Spontaneously Hypertensive ◽  
Polymerase Chain ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide ◽  
Stimulation Of

A focal infarction produced by occlusion of the middle cerebral artery (MCAO) in spontaneously hypertensive rats induced expression of inducible nitric oxide synthase (iNOS) mRNA, measured by competitive reverse transcription-polymerase chain reaction. The mRNA appeared simultaneously in the ischemic core and penumbra at 8 h, peaked between 14 and 24 h, and disappeared by 48 h. At 24 h, inducible nitric oxide synthase (iNOS)-like immunoreactivity was present in the endothelium of cerebral microvessels and in scattered cells, probably representing leukocytes or activated microglia. Electrical stimulation of the cerebellar fastigial nucleus (FN) for 1 h, 48 h before MCAO, reduced infarct volumes by 45% by decreasing cellular death in the ischemic penumbra. It also reduced by >90% the expression of iNOS mRNA and protein in the penumbra, but not core, and decreased by 44% the iNOS enzyme activity. We conclude that excitation of neuronal networks represented in the cerebellum elicits a conditioned central neurogenic neuroprotection associated with the downregulation of iNOS mRNA and protein. This neuroimmune interaction may, by blocking the expression of iNOS, contribute to neuroprotection.

Induction of Nitric Oxide Synthase in Human Mesangial Cells

1993 ◽  
Vol 193 (3) ◽  
pp. 1269-1274 ◽  
Author(s):  
A.G. Nicolson ◽  
N.E. Haites ◽  
N.G. Mckay ◽  
H.M. Wilson ◽  
A.M. Macleod ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Oxide Synthase

scholarly journals Role of Tetrahydrobiopterin Availability in the Regulation of Nitric-oxide Synthase Expression in Human Mesangial Cells

1996 ◽  
Vol 271 (24) ◽  
pp. 14290-14295 ◽  
Author(s):  
Marta Saura ◽  
Dolores Pérez-Sala ◽  
Francisco J. Cañada ◽  
Santiago Lamas
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Oxide Synthase

Inducible nitric oxide synthase subserves cholinergic vasodilation in retina

2005 ◽  
Vol 22 (3) ◽  
pp. 371-377 ◽  
Author(s):  
ALEJANDRO BERRA ◽  
SABRINA GANZINELLI ◽  
MARIO SARAVIA ◽  
ENRI BORDA ◽  
LEONOR STERIN-BORDA
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Retinal Vessel ◽  
Inos Mrna ◽  
Mrna Levels ◽  
Mrna Gene ◽  
Oxide Synthase ◽  
Mrna Gene Expression ◽  
Stimulation Of

In this paper, we investigate the role of muscarinic acetylcholine receptor (mAChR) activity in the regulation of inducible (i) nitric oxide synthase (iNOS) expression and activity. The signaling pathway involved is also examined. These experiments also provide a link between mAChR activation and the nitric oxide (NO)-dependent regulation of retinal vascular diameter. The diameter of the retinal vessels at a distance of 1 disc diameter from the center of the optic disc was measured in rats using digital retinal photography, and both iNOS-mRNA gene expression and NOS were specifically measured using RT-PCR and [U-14C] citrulline assays, respectively. Stimulation of M1 and M3 mAChR with carbachol caused an increase in vessel diameter, in iNOS-mRNA levels and in NOS activity in the retina. Aminoguanidine, an inhibitor of iNOS, attenuated all these effects. Inhibitors of phospholipase C (PLC) and protein kinase C (PKC) but not calcium/calmodulin (CaM) prevented the muscarinic-dependent increase in iNOS-mRNA levels. The results obtained suggest that the activation of mAChR increases retinal vessel diameters by increasing the production of nitric oxide (NO) through iNOS activation and iNOS-mRNA gene expression. The mechanism appears to occur secondarily to stimulation of PLC and PKC enzymatic activity.

Tyrosine kinase activation is necessary for inducible nitric oxide synthase expression by interleukin-1 beta

1995 ◽  
Vol 269 (1) ◽  
pp. C55-C59 ◽  
Author(s):  
T. Tetsuka ◽  
A. R. Morrison
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Mesangial Cells ◽  
Interleukin 1 ◽  
Inos Mrna ◽  
Nitrite Production ◽  
Oxide Synthase

The inflammatory cytokine interleukin-1 (IL-1) induces the inducible form of nitric oxide synthase (iNOS) with an increase in nitric oxide in rat mesangial cells. However, the cellular mechanisms that underlie the induction of iNOS by IL-1 beta in mesangial cells has not been clarified. Because we have shown that tyrosine kinase inhibitors attenuate IL-1 beta-induced cyclooxygenase expression and prostaglandin production, we investigated the effect of tyrosine kinase inhibitors on IL-1 beta-induced nitrite production and iNOS mRNA expression in rat mesangial cells. The tyrosine kinase inhibitors genistein and herbimycin A attenuated IL-1 beta-induced nitrite production in a dose-dependent manner. In addition, both of these inhibitors blocked IL-1 beta-induced iNOS mRNA expression. These data suggest that tyrosine kinase(s) plays a central role in IL-1 beta signaling to induce iNOS in rat mesangial cells.

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