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A Ianaro

Publications and source records attributed to A Ianaro.

29 records · Page 2Linked to original sources
PubMed1999

Nuclear factor-kappaB activation mediates inducible nitric oxide synthase expression in carrageenin-induced rat pleurisy.

We studied the involvement of nuclear factor-kappaB (NF-kappaB) in the regulation of inducible nitric oxide synthase expression in carrageenin-induced rat pleurisy. Injection of 0.2 ml of 1% lambda-carrageenin into the pleural cavity of male Wistar rats caused after 6 h: (a) exudate formation and leukocyte migration into the pleural cavity; (b) inducible NO synthase protein expression and accumulation of NO2- plus NO3- in pleural exudate; (c) increase in p50/p65 nuclear level as well as NF-kappaB/DNA binding activity. Treatment of rats with pyrrolidine dithiocarbamate (10, 30, and 100 mg/kg) and N-alpha-p-tosyl-L-lysine chloromethylketone (30 mg/kg), two inhibitors of NF-kappaB activation, given subcutaneously concomitantly with carrageenin, caused a significant inhibition of all the parameters assayed. These results suggest that in carrageenin-induced rat pleurisy the activation of NF-kappaB plays a key role in inducible NO synthase protein expression and in the development of inflammatory response.

Animals↗
PubMed1998

Relationship between nitric oxide and prostaglandins in carrageenin pleurisy.

The correlation between endogenous nitric oxide (NO) generation and prostaglandin biosynthesis was studied in rat carrageenin pleurisy induced by the injection of 0.2 mL of 1% lambda-carrageenin into the pleural cavity. The pleural exudate was collected at 4 hr and the amounts of NO2- + NO3- (NOx) and prostaglandin E2 (PGE2) measured. The NOx present in the inflammatory exudate was determined by measuring the NO2- with the Griess reaction, after the reduction of NO3- to NO2- using acid-washed cadmium powder. PGE2 was measured by radioimmunoassay. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 1-3-10 mg/kg subcutaneously) reduced NOx by 20 +/- 7%, 41 +/- 6% and 55 +/- 9% (P < 0.01) and PGE2 by 9 +/- 6%, 41 +/- 11% and 74 +/- 9% (P < 0.001). Conversely, L-arginine (300 mg/kg SC) increasedNOx by 39 +/- 7% (P < 0.01) and PGE2 by 78 +/- 6% (P < 0.001). The NO scavenger haemoglobin (Hb), coinjected into the pleural cavity (3 mg/site) with carrageenin, produced a parallel inhibition of NOx (65 +/- 16%, P < 0.001) and PGE2 (71 +/- 18%, P < 0.001). The soluble guanylate cyclase inhibitor methylene blue (Mb; 2 mg/site) had no effect. Moreover haemoglobin, but not methylene blue, was able to significantly suppress the L-arginine-induced increase of both NOx and PGE2. In each pleural exudate, independently from the animal treatment, the amount of NOx was highly correlated to the amount of PGE2 (r = 0.93, P < 0.001). These results suggest that in rat carrageenin pleurisy the modulation of the L-arginine:NO pathway results in a parallel modulation of prostaglandin biosynthesis. The interaction between cyclooxygenase and the NO pathway may represent an important mechanism for the modulation of the inflammatory response.

Animals↗
PubMed1998

Nitric oxide inhibits neutrophil infiltration in the reverse passive arthus reaction in rat skin.

The role of nitric oxide (NO) in the reverse passive Arthus reaction elicited in the rat skin has been studied. The reverse passive Arthus reaction was modulated by test compounds given by intradermal injection in combination with anti-bovine serum albumin antibody. L-arginine (1.5-15 micromol/site) and the NO donor [1-hydroxy-2-oxo-3,3-bis (3-amonoethyl)- 1-triazenel (NOC-18; 1-10 micromol/site) both significantly reduced neutrophil infiltration and increased plasma leakage. The NO scavenger haemoglobin (30 and 100 micromol/site) did not affect oedema formation but increased neutrophil infiltration and attenuated the effects of L-arginine. The non-selective nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl ester (0.3-100 nmol/site) and N(G)-monomethyl-L-arginine (0.3-100 nmol/site) or the relatively selective inhibitors of the inducible NO synthase aminoguanidine (30-1000 nmol/site) and S-methylthiourea (3-1000 nmol/site) significantly reduced plasma leakage when given at high doses. Furthermore all these inhibitors exhibited a dose-related biphasic effect on neutrophil infiltration which was significantly increased by low doses and reduced by high doses, while intermediate doses had no effect. Phenylpropanolamine, a sympathomimetic vasoconstrictor (15-60 micromol/site), dose-dependently reduced both oedema formation and neutrophil infiltration. These results provide evidence for a relevant role of NO as a modulator of rat dermal reverse passive Arthus reaction and suggest that at the vascular level NO controls primarily the interaction between leucocyte and endothelial cell rather than the vascular permeability.

Animals↗
PubMed1997

Inhibition of inducible nitric oxide synthase gene expression by glucocorticoid-induced protein(s) in lipopolysaccharide-stimulated J774 cells.

Glucocorticoids inhibit inducible-type NO synthase activity in a variety of cell types. We report here that proteins recovered from the medium of dexamethasone-treated J774 macrophages (1, 10, 100 microg/ml) inhibited lipopolysaccharide-stimulated nitrite generation by 10.0 +/- 3.0%, 32.3 +/- 5.3% and 55.0 +/- 6.0%, respectively, and inducible NO synthase mRNA expression in these cells. Immunoblotting analysis of crude and partially purified glucocorticoid-induced proteins with an anti-lipocortin-1 polyclonal antiserum revealed the presence of lipocortin-1-like immunoreactive species with a molecular mass of 35-37 kDa. Furthermore, inhibition of lipopolysaccharide-induced nitrite production by glucocorticoid-induced proteins in J774 cells was reversed by addition of anti-lipocortin-1 neutralizing polyclonal antibody (1:60 dilution; 4 h before lipopolysaccharide). Comparison of glucocorticoid-induced proteins inhibition of both nitrite production and inducible NO synthase mRNA expression suggests that these effects result mainly from inhibition of lipopolysaccharide-mediated inducible NO synthase gene expression. These results indicate that negative regulation of inducible NO synthase by glucocorticoids is, at least in part, mediated by glucocorticoid-induced proteins that involve also members of the lipocortin-like superfamily.

Animals↗
PubMed1995

Endogenous nitric oxide increases prostaglandin biosynthesis in carrageenin rat paw oedema.

The influence of endogenous nitric oxide (NO) on prostaglandin biosynthesis in rat carrageenin oedema was studied. Oedema formation and prostaglandin E2 generation in the inflamed paw were both increased by L- but not D-arginine and reduced by the NO synthase inhibitor, L-NG-nitro arginine methyl ester, and the NO scavenger, haemoglobin. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. These results suggest that endogenous NO modulates carrageenin oedema by increasing prostaglandin biosynthesis at the inflammatory site through a cGMP-independent mechanism.

Animals↗
PubMed1995

Modulation by nitric oxide of prostaglandin biosynthesis in the rat.

1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw). 6. In LPS-treated rats (6 mg kg-1, i.p.) doses of AA inactive in normal animals produced a remarkable oedema which was reduced by L-NAME or Hb, unaffected by Mb and increased by L-arginine.7. These results demonstrate that NO increases prostaglandin biosynthesis in vivo through a guanosine 3': 5'-cyclic monophosphate (cyclic GMP)-independent mechanism and suggest that the interaction between NO synthase and cyclo-oxygenase (COX) pathways may represent an important mechanism for the modulation of the inflammatory response.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Expression of TGF-beta in attenuated Salmonella typhimurium: oral administration leads to the reduction of inflammation, IL-2 and IFN-gamma, but enhancement of IL-10, in carrageenin-induced oedema in mice.

Mice injected with carrageenin in the footpad developed local inflammation which peaked at 48 hr. This was significantly reduced in mice inoculated orally with an attenuated Salmonella construct expressing transforming growth factor-beta (TGF-beta). Administration of the Salmonella construct alone had no effect on inflammation. High levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were secreted by draining lymph node cells from mice injected with carrageenin following stimulation in vitro. Prior inoculation with Salmonella enhanced the production of IL-2 and IFN-gamma from the draining lymph node cells. Administration of the Salmonella-TGF-beta construct significantly inhibited the production of these cytokines. In contrast, IL-10 only was secreted from draining lymph node cells of animals inoculated with the Salmonella-TGF-beta construct. Thus, oral administration of TGF-beta can significantly inhibit local inflammation and alter the cytokine secretion pattern of cells from lymph nodes draining the site of inflammation.

Administration, Oral↗
PubMed1994

A nitric oxide synthase inhibitor reduces inflammation, down-regulates inflammatory cytokines and enhances interleukin-10 production in carrageenin-induced oedema in mice.

Mice injected in the footpad with carrageenin developed local inflammation which peaked at 48 hr. This delayed-type footpad swelling was significantly reduced in mice injected intraperitoneally (i.p.) with a specific nitric oxide (NO) synthase inhibitor, L-NGmonomethyl-arginine (L-NMMA). The draining lymph node (DLN) cells from mice injected 48 hr previously with carrageenin produced significantly higher levels of proliferation and interleukin-1 (IL-1), IL-2, IL-6 and interferon-gamma (IFN-gamma), but less IL-10, compared to cells from saline-injected controls, when stimulated with concanavalin A (Con A) in vitro. Treatment of the carrageenin-injected mice with L-NMMA had little effect on the proliferative response of the DLN cells, but significantly reduced the production of IL-1, IL-2, IL-6 and IFN-gamma, and increased the secretion of IL-10. These data demonstrate that NO plays a significant role in local inflammation and the pattern of cytokines induced in this model.

Animals↗
PubMed1992

Modulation of acute inflammation by endogenous nitric oxide.

The role of endogenous nitric oxide (NO) in acute inflammation was investigated using two inhibitors of NO synthase (NG-nitro-L-arginine methyl ester(L-NAME) and NG-monomethyl-L-arginine (L-NMMA)) as well as L- or D-arginine. The effect of test compounds was studied on the carrageenin-induced increase in vascular permeability in rat skin and in dextran- and carrageenin-induced paw oedema. Both L-NAME and L-NMMA dose dependently inhibited the increase in vascular permeability and oedema formation. L- but not D-arginine increased these inflammatory responses and reversed the inhibitory effects of L-NAME and L-NMMA. In dexamethasone-treated rats L-arginine enhanced the dextran-induced oedema and the early phase of carrageenin-induced oedema but did not modify the inhibition by dexamethasone of the late phase of carrageenin-induced oedema. These results suggest that endogenous NO is released at the site of acute inflammation and modulates oedema formation. Depending on the time course or on the type of inflammation, NO may be predominantly generated by the constitutive or by the inducible NO synthase.

Acute Disease↗
PubMedDate not supplied

Clarithromycin in rheumatoid arthritis patients not responsive to disease-modifying antirheumatic drugs: an open, uncontrolled pilot study.

OBJECTIVE: In 1996 we found by serendipity that 2 patients with rheumatoid arthritis (RA) who were taking clarithromycin (CM) to eradicate Helicobacter pylori experienced a regression of their RA symptoms. Following this observation, we tested the hypothesis that this reduction in symptoms could have been caused by CM administration. METHODS: We performed a 6-month, open, uncontrolled pilot study on 18 patients (14 females and 4 males, mean age 62 yrs.) with RA who had previously received DMARDs (mean 2.6) and discontinued the treatment at least one month earlier because lack of efficacy or severe side effects. Patients were treated with CM at the dose of 500 mg twice per day for the first 10 days, followed by a daily maintenance dose of 250 mg twice per day. RESULTS: 4/18 patients did not complete the treatment, 2/18 were not responsive to the treatment and 2/18 discontinued the treatment. Following ACR criteria the improvement was: 10 patients ACR 20; 6 patients ACR 50; and 2 patients ACR 70. The remaining 4 patients did not reach ACR 20 since either the number of tender or swollen joints was not to the level required. Reductions in PGE2 and soluble phospholipase A2 plasma levels were closely related to CM plasma levels. CONCLUSIONS: Ourfindings suggest that CM treatment can be beneficial in those patients who are not responsive to or cannot tolerate DMARDs. No definitive conclusions can be drawn based on the present study, due to the small sample size involved.

Adult↗