The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform

Claire Lugnier - One of the best experts on this subject based on the ideXlab platform.

  • Disease Progression in MRL/lpr Lupus-Prone Mice Is Reduced by NCS 613, a Specific Cyclic Nucleotide Phosphodiesterase Type 4 (PDE4) Inhibitor
    2016
    Co-Authors: Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFa secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, Denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/ J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtyp

  • Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor.
    PloS one, 2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, Denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC50 = 1.4 nM) than the other subtypes (PDE4A, IC50 = 44 nM; PDE4B, IC50 = 48 nM; and PDE4D, IC50 = 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (Ki = 148 nM) in comparison to rolipram (Ki = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease.

  • Pentoxifylline, Denbufylline and NCS 613 treatment effects on proteinuria and survival rate of MRL/lpr mice.
    2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Four groups of MRL/lpr mice were injected via the i.v. route at 5, 7, 9 and 13 weeks with either 100 µL of PBS-10% ethanol (control, n = 10), or 100 µg pentoxifylline in 100 µL PBS-10% ethanol (n = 10), or 100 µg Denbufylline in 100 µL PBS-10% ethanol (n = 10), or 30 µg NCS 613 in 100 µL PBS-10% ethanol (n = 8). Proteinuria was measured as described in the Methods section at weeks 10, 14, 18 and 20 are represented for each mouse. Each symbol represents an individual mouse and horizontal lines indicate the median. Closed symbols represent PBS-treated mice and open symbols represent inhibitors-treated mice (pentoxifylline, Denbufylline and NCS 613). Because PBS-treated-MRL/lpr mice present a high mortality, dead mice were considered to have a proteinuria >2000 mg/dL (the level measured the week before their death). Survival rate is expressed as the percentage of surviving mice with time expressed in weeks. *, P

  • PDE inhibitor treatment effects on ex vivo LPS-induced TNFα secretion by PBLs from MRL/lpr mice.
    2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Four groups of 7 MRL/lpr mice each were injected i.v. at 5, 7, 9 and 13 weeks with either 100 µL of PBS-10% ethanol (control), or 100 µg pentoxifylline in 100 µL PBS-10% ethanol, or 100 µg Denbufylline in 100 µL PBS-10% ethanol, or 30 µg NCS 613 in 100 µL PBS-10% ethanol. Blood samples were collected from 14 week-old treated mice. PBLs pooled from seven mice of each group were purified and cultured in the presence of LPS, and TNFα secretion was determined by ELISA 24 h later. The results are expressed as the mean concentration (pg/mL) ±s.e.m. of duplicate cultures. *, P

Kenichi Miyamoto - One of the best experts on this subject based on the ideXlab platform.

  • synthesis and cyclic amp phosphodiesterase 4 isoenzyme inhibitory activity of heterocycle condensed purines
    Chemical & Pharmaceutical Bulletin, 2002
    Co-Authors: Hirokazu Suzuki, Kenichi Miyamoto, Manabu Yamamoto, Susumu Shimura, Kenji Yamamoto, Hiroyuki Sawanishi
    Abstract:

    To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP phosphodiesterase 4 (PDE4), a series of heterocycle [a]-, [b]-, [c,d]-, and [i]-condensed purines were designed and synthesized. Although all compounds did not display PDE1 and PDE3 inhibitory activities, several heterocycle [i]-condensed purines strongly inhibited PDE4. Especially, dl-3,4-dipropyl-8-methyl-4,5,7,8-tetrahydro-1H-imidazo[2,1-i]purin-5-one (dl-7c) exhibited comparable PDE4 inhibitory activity (IC(50)=1.9 microM) to rolipram and Denbufylline (DBF).

  • selective inhibitors of cyclic amp specific phosphodiesterase heterocycle condensed purines
    Journal of Medicinal Chemistry, 1997
    Co-Authors: Hiroyuki Sawanishi, Kenichi Miyamoto, Hirokazu Suzuki, Yoshihiro Waki, Shohei Kasugai, Keiichi Ohya, Shinya Yamamoto, Nagao Suzuki, Kenzo Takagi
    Abstract:

    To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), a series of heterocycle-condensed purines were designed and synthesized. Some of these new compounds had similar or more potent and selective inhibitory activity against PDE IV than known PDE IV inhibitors. The tracheal-relaxant activity of these compounds was closely correlated with their PDE IV-inhibitory activity. Moreover, these purine analogues did not have any positive-chronotropic action or adenosine-antagonistic action on isolated heart preparations, which are the particular adverse reactions of alkylxanthines. Among them, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]-purin-5-one (1c), which was the most selective and potent PDE IV inhibitor, did not cause emesis in Suncus murinus at a dosage range of 10-100 mg/kg (po), while an imidazole analogue of 1c (4c) and known PDE IV inhibitors such as rolipram and Denbufylline caused emesis even at 10 or 30 mg/kg.

  • reduction of bone loss by Denbufylline an inhibitor of phosphodiesterase 4
    Biochemical Pharmacology, 1997
    Co-Authors: Kenichi Miyamoto, Yoshihiro Waki, Takashi Horita, Shohei Kasugai, Keiichi Ohya
    Abstract:

    The effects of Denbufylline, a xanthine derivative with selective inhibitory activity on the phosphodiesterase (PDE) 4 isoenzyme, on bone loss in Walker 256/S-bearing rats and on mineralized nodule formation and osteoclastlike cell formation in bone marrow culture systems were examined. Serial oral administrations of Denbufylline inhibited the decrease in the bone mineral density of femurs from Walker 256/S-bearing rats, without influence on the healthy rats. Denbufylline restored the bone mass and the number of osteoclasts and osteoblasts per trabecular surface in the femur metaphysis. Among PDE inhibitors, only PDE4-selective inhibitors increased the number of mineralized nodules and decreased the number of osteoclastlike cells in the in vitro bone marrow culture systems, and dibutyryl cyclic AMP mimicked these effects in the in vitro systems. These results suggest that the PDE4 isoenzyme may play an important role in bone turnover through cyclic AMP and that its inhibitors are candidates for therapeutic drugs for the bone loss diseases.

  • negative inotropic action of Denbufylline through interfering with the calcium channel independently of its pde iv inhibitory activity in guinea pig ventricle papillary muscles
    Journal of Pharmacology and Experimental Therapeutics, 1996
    Co-Authors: Fujiko Sanae, Shinji Ohmae, D Kobayashi, K Takag, Kenichi Miyamoto
    Abstract:

    The inotropic actions of xanthine derivatives with long alkyl chains were investigated in guinea pig ventricular papillary muscle. A potent and nonselective phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine, elicited a positive inotropy and inhibited the negative inotropic effects of calcium channel inhibitors, as did a selective PDE III inhibitor, amrinone, and these effects were canceled by a protein kinase inhibitor, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89). However, 1,3-di-n-butyl-7-(2'oxopropyl)xanthine (Denbufylline) and 1-n-butyl-3-n-propylxanthine (XT-044), which have potent and selective PDE IV-inhibitory activities, showed negative inotropic actions that became more potent in the presence of H-89. Denbufylline abolished the late restoration phase induced by ryanodine. This xanthine derivative attenuated the effects of both the calcium channel acting agents Bay K 8644 and verapamil, without interaction with caffeine and dihydropyridine calcium channel inhibitors, and Denbufylline had little direct influence on the specific binding of [(3)H]azidopine and [(3)H]desmethoxyverapamil to cardiac membranes. A nonxanthine PDE IV inhibitor, Ro 20-1724, did not affect the inotropic actions of calcium channel inhibitors. The attenuation by Denbufylline or XT-044 of the negative inotropic action of verapamil was not influenced by treatment with H-89. These results suggest that in the ventricular papillary muscle, these xanthine derivatives elicit negative inotropy by acting on a verapamil-sensitive site of the calcium channel without involving their PDE-inhibitory activity.

  • A xanthine derivative Denbufylline inhibits negative inotropic response to verapamil in guinea pig ventricular papillary muscles, independent of its phosphodiesterase inhibitory activity.
    Japanese journal of pharmacology, 1995
    Co-Authors: Fujiko Sanae, Shinji Ohmae, Kenzo Takagi, Kenichi Miyamoto
    Abstract:

    A phosphodiesterase (PDE) III inhibitor, amrinone, inhibited both the negative inotropic actions of verapamil and nicardipine in guinea pig ventricular papillary muscle; this effect was canceled by the protein kinase A inhibitor H-89. The PDE IV inhibitor 1, 3-di-n-butyl-7-(2’-oxopropyl)xanthine (Denbufylline), which elicited a negative inotropic action by itself, attenuated the action of verapamil up to 10 μM, without any interaction, with nicardipine. The attenuation by Denbufylline was not influenced by H-89. This suggests that in the ventricular papillary muscle, Denbufylline acts on some verapamil-sensitive site(s) in the membrane and interferes with the calcium channel function without involvement of its PDE inhibitory activity.

B S Hsieh - One of the best experts on this subject based on the ideXlab platform.

  • dual regulation of tumor necrosis factor alpha induced ccl2 monocyte chemoattractant protein 1 expression in vascular smooth muscle cells by nuclear factor kappab and activator protein 1 modulation by type iii phosphodiesterase inhibition
    Journal of Pharmacology and Experimental Therapeutics, 2004
    Co-Authors: Yungming Chen, Wenchih Chiang, Shueiliong Lin, Tunjun Tsai, B S Hsieh
    Abstract:

    Monocyte/macrophage infiltration to the subendothelial space of arterial wall is a critical initial step in atherogenesis, in which CC chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1) is thought to play a key role. This study investigated the effectiveness of phosphodiesterase inhibitors, including the nonselective pentoxifylline (PTX) and the selective type III (cilostamide) and type IV (Denbufylline) inhibitors, on cytokine-induced CCL2/MCP-1 production in cultured rat vascular smooth muscle cells (VSMCs), and the signal transduction mechanisms whereby they act. Our results showed that tumor necrosis factor (TNF)-α induced a marked increase in CCL2/MCP-1 production in dose- and time-dependent manners. 2-(2-Amino-3-methoxyphenyl)- 4H -1-benzopyran-4-one (PD98059), 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio) butadiene (U0126) [both inhibitors of p42/44 mitogen-activated protein kinase (MAPK) kinase], and anthra[1hyphen]9-cd]pyrazol-6( 2H )-one (SP600125) [an inhibitor of c-Jun NH2-terminal kinases (JNKs)] attenuated TNF-α-induced CCL2/MCP-1 production, without affecting I-κBα degradation or p65/nuclear factor-κB (NF-κB) nuclear translocation. PD98059 abolished TNF-α-activated p42/44 MAPK phosphorylation and c-Fos up-regulation, whereas SP600125 inhibited TNF-α-activated JNK and c-Jun phosphorylation. The NF-κB inhibitor carbobenzoxy-l-leucyl-l-leucyl-l-leucinal (MG132) attenuated TNF-α-induced CCL2/MCP-1 production in the presence of increased phospho-JNK and phospho-c-Jun levels. When SP600125 was added simultaneously, MG132 completely inhibited TNF-α-induced CCL2/MCP-1 production. Finally, the pretreatment of VSMCs with PTX or cilostamide, but not Denbufylline, reduced TNF-α-induced CCL2/MCP-1 production, which was preceded by attenuation of p65/NF-κB nuclear translocation, p42/44 MAPK, and JNK-c-Jun phosphorylation, and c-Fos up-regulation. These data indicate that TNF-α-stimulated CCL2/MCP-1 production in rat VSMCs is dually regulated by activator protein-1 (AP-1) and NF-κB pathways, and inhibition of type III phosphodiesterase contributes substantially to the suppressive effect of PTX on CCL2/MCP-1 production via down-regulation of AP-1 and NF-κB signals.

Fanny Monneaux - One of the best experts on this subject based on the ideXlab platform.

  • Disease Progression in MRL/lpr Lupus-Prone Mice Is Reduced by NCS 613, a Specific Cyclic Nucleotide Phosphodiesterase Type 4 (PDE4) Inhibitor
    2016
    Co-Authors: Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFa secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, Denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/ J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtyp

  • Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor.
    PloS one, 2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, Denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC50 = 1.4 nM) than the other subtypes (PDE4A, IC50 = 44 nM; PDE4B, IC50 = 48 nM; and PDE4D, IC50 = 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (Ki = 148 nM) in comparison to rolipram (Ki = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease.

  • Pentoxifylline, Denbufylline and NCS 613 treatment effects on proteinuria and survival rate of MRL/lpr mice.
    2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Four groups of MRL/lpr mice were injected via the i.v. route at 5, 7, 9 and 13 weeks with either 100 µL of PBS-10% ethanol (control, n = 10), or 100 µg pentoxifylline in 100 µL PBS-10% ethanol (n = 10), or 100 µg Denbufylline in 100 µL PBS-10% ethanol (n = 10), or 30 µg NCS 613 in 100 µL PBS-10% ethanol (n = 8). Proteinuria was measured as described in the Methods section at weeks 10, 14, 18 and 20 are represented for each mouse. Each symbol represents an individual mouse and horizontal lines indicate the median. Closed symbols represent PBS-treated mice and open symbols represent inhibitors-treated mice (pentoxifylline, Denbufylline and NCS 613). Because PBS-treated-MRL/lpr mice present a high mortality, dead mice were considered to have a proteinuria >2000 mg/dL (the level measured the week before their death). Survival rate is expressed as the percentage of surviving mice with time expressed in weeks. *, P

  • PDE inhibitor treatment effects on ex vivo LPS-induced TNFα secretion by PBLs from MRL/lpr mice.
    2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Four groups of 7 MRL/lpr mice each were injected i.v. at 5, 7, 9 and 13 weeks with either 100 µL of PBS-10% ethanol (control), or 100 µg pentoxifylline in 100 µL PBS-10% ethanol, or 100 µg Denbufylline in 100 µL PBS-10% ethanol, or 30 µg NCS 613 in 100 µL PBS-10% ethanol. Blood samples were collected from 14 week-old treated mice. PBLs pooled from seven mice of each group were purified and cultured in the presence of LPS, and TNFα secretion was determined by ELISA 24 h later. The results are expressed as the mean concentration (pg/mL) ±s.e.m. of duplicate cultures. *, P

Sylviane Muller - One of the best experts on this subject based on the ideXlab platform.

  • Disease Progression in MRL/lpr Lupus-Prone Mice Is Reduced by NCS 613, a Specific Cyclic Nucleotide Phosphodiesterase Type 4 (PDE4) Inhibitor
    2016
    Co-Authors: Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFa secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, Denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/ J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtyp

  • Disease progression in MRL/lpr lupus-prone mice is reduced by NCS 613, a specific cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitor.
    PloS one, 2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, Denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC50 = 1.4 nM) than the other subtypes (PDE4A, IC50 = 44 nM; PDE4B, IC50 = 48 nM; and PDE4D, IC50 = 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (Ki = 148 nM) in comparison to rolipram (Ki = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease.

  • Pentoxifylline, Denbufylline and NCS 613 treatment effects on proteinuria and survival rate of MRL/lpr mice.
    2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Four groups of MRL/lpr mice were injected via the i.v. route at 5, 7, 9 and 13 weeks with either 100 µL of PBS-10% ethanol (control, n = 10), or 100 µg pentoxifylline in 100 µL PBS-10% ethanol (n = 10), or 100 µg Denbufylline in 100 µL PBS-10% ethanol (n = 10), or 30 µg NCS 613 in 100 µL PBS-10% ethanol (n = 8). Proteinuria was measured as described in the Methods section at weeks 10, 14, 18 and 20 are represented for each mouse. Each symbol represents an individual mouse and horizontal lines indicate the median. Closed symbols represent PBS-treated mice and open symbols represent inhibitors-treated mice (pentoxifylline, Denbufylline and NCS 613). Because PBS-treated-MRL/lpr mice present a high mortality, dead mice were considered to have a proteinuria >2000 mg/dL (the level measured the week before their death). Survival rate is expressed as the percentage of surviving mice with time expressed in weeks. *, P

  • PDE inhibitor treatment effects on ex vivo LPS-induced TNFα secretion by PBLs from MRL/lpr mice.
    2012
    Co-Authors: Thérèse Keravis, Issaka Yougbaré, Fanny Monneaux, Lucien Gazi, Jean-jacques Bourguignon, Sylviane Muller, Claire Lugnier
    Abstract:

    Four groups of 7 MRL/lpr mice each were injected i.v. at 5, 7, 9 and 13 weeks with either 100 µL of PBS-10% ethanol (control), or 100 µg pentoxifylline in 100 µL PBS-10% ethanol, or 100 µg Denbufylline in 100 µL PBS-10% ethanol, or 30 µg NCS 613 in 100 µL PBS-10% ethanol. Blood samples were collected from 14 week-old treated mice. PBLs pooled from seven mice of each group were purified and cultured in the presence of LPS, and TNFα secretion was determined by ELISA 24 h later. The results are expressed as the mean concentration (pg/mL) ±s.e.m. of duplicate cultures. *, P