Phosphodiesterase 7A inhibitor ASB16165 suppresses proliferation and cytokine production of NKT cells

Goto, Megumi; Murakawa, Masao; Kadoshima-Yamaoka, Kumiko; Tanaka, Yoshitaka; Inoue, Hidekazu; Murafuji, Hidenobu; Hayashi, Yasuhiko; Miura, Kazuhiro; Nakatsuka, Takashi; Nagahira, Kazuhiro; Chamoto, Kenji; Fukuda, Yoshiaki; Nishimura, Takashi

doi:10.1016/j.cellimm.2009.04.005

Cited by 28 publications

(14 citation statements)

References 28 publications

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“…Although the mechanism by which GLP-1 suppresses the expression of pro- inflammatory and profibrotic mediators warrants further studies, it is possible that this effect is also mediated by cAMP induction. Indeed, it has already been shown that elevated levels of cAMP reduce expression of pro-inflammatory cytokines in NKT and dendritic cells by directly inhibiting transcription of PAI-1 [31,32].…”

Section: Discussionmentioning

confidence: 98%

Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase

Ben-Shlomo

Zvibel

Shnell

et al. 2011

Journal of Hepatology

265

206

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Section: Discussionmentioning

confidence: 98%

Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase

Ben-Shlomo

Zvibel

Shnell

et al. 2011

Journal of Hepatology

265

206

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“…The involvement of other PDEs in cell proliferation elsewhere has been shown previously. For example, a specific inhibitor of PDE7 decreased proliferation of murine natural killer T cells [34], and the PDE inhibitor pentoxifylline decreased proliferation of the rat epithelial cell line IEC18 [35].…”

Section: Discussionmentioning

confidence: 99%

β2-Agonist Induced cAMP Is Decreased in Asthmatic Airway Smooth Muscle Due to Increased PDE4D

et al. 2011

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Background and ObjectiveAsthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known.ObjectiveTo characterize the potential defect in β-agonist induced cAMP in ASM derived from asthmatic in comparison to non-asthmatic subjects and to investigate its mechanism.MethodsWe examined β2-adrenergic (β2AR) receptor expression and basal β-agonist and forskolin (direct activator of adenylyl cyclase) stimulated cAMP production in asthmatic cultured ASM (n = 15) and non-asthmatic ASM (n = 22). Based on these results, PDE activity, PDE4D expression and cell proliferation were determined.ResultsIn the presence of IBMX, a pan PDE inhibitor, asthmatic ASM had ∼50% lower cAMP production in response to isoproterenol, albuterol, formoterol, and forskolin compared to non-asthmatic ASM. However when PDE4 was specifically inhibited, cAMP production by the agonists and forskolin was normalized in asthmatic ASM. We then measured the amount and activity of PDE4, and found ∼2-fold greater expression and activity in asthmatic ASM compared to non-asthmatic ASM. Furthermore, inhibition of PDE4 reduced asthmatic ASM proliferation but not that of non-asthmatic ASM.ConclusionDecreased β-agonist induced cAMP in ASM from asthmatics results from enhanced degradation due to increased PDE4D expression. Clinical manifestations of this dysregulation would be suboptimal β-agonist-mediated bronchodilation and possibly reduced control over increasing ASM mass. These phenotypes appear to be “hard-wired” into ASM from asthmatics, as they do not require an inflammatory environment in culture to be observed.

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“…However, the study with the PDE7A-deficiet mice has demonstrated that PDE7A might not be necessary for the activation of T cells [14]. In this respect, it should be noted that PDE7A inhibitors impair cytokine production by T cells [15] and NKT cells [16].…”

Section: Introductionmentioning

confidence: 97%

Inhibition of phosphodiesterase 7A ameliorates Concanavalin A-induced hepatitis in mice

Goto¹,

Tanaka²,

Murakawa³

et al. 2009

International Immunopharmacology

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Phosphodiesterase 7A inhibitor ASB16165 suppresses proliferation and cytokine production of NKT cells

Cited by 28 publications

References 28 publications

Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase

Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase

β2-Agonist Induced cAMP Is Decreased in Asthmatic Airway Smooth Muscle Due to Increased PDE4D

Inhibition of phosphodiesterase 7A ameliorates Concanavalin A-induced hepatitis in mice

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