Different effects of soluble and particulate guanylyl cyclases on expression of inflammatory cytokines in rat peripheral blood mononuclear cells

Mitkiewicz, Małgorzata; Kuropatwa, Marianna; Kurowska, Ewa; Gorczyca, Wojciech

doi:10.1016/j.imbio.2010.06.006

Cited by 8 publications

(12 citation statements)

References 44 publications

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“…These findings are in line with previous reports demonstrating that both innate and adaptative immune responses are regulated by cGMP/PKG signaling. Indeed, compounds elevating its intracellular concentrations decreased the secretion of inflammatory proteins by activated monocytes/macrophages and endothelial cells . The PKG1 transgenic mouse model, overexpressing PKG1, generated to evaluate ischemia‐reperfusion‐induced kidney injury, showed decreased inflammatory cell infiltration and cytokines expression in the kidney .…”

Section: Discussionmentioning

confidence: 99%

PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS

et al. 2013

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In vitro treatment with tadalafil or vardenafil on hBPH reduced IL-8 secretion induced by either TNFα or metabolic factors, including oxidized low-density lipoprotein, oxLDL, to the same extent as a PDE5-insensitive PKG agonist Sp-8-Br-PET-cGMP. These effects were reverted by the PKG inhibitor KT5823, suggesting a cGMP/PKG-dependency. Treatment with tadalafil or vardenafil significantly suppressed oxLDL receptor (LOX-1) expression. Histological evaluation of anti-CD45 staining (CD45 score) in prostatectomy specimens of BPH patients showed a positive association with MetS severity. Reduced HDL-cholesterol and elevated triglycerides were the only MetS factors significantly associated with CD45 score. In the MetS cohort there was a significant lower CD45 score in the vardenafil-arm versus the placebo-one.

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Section: Discussionmentioning

confidence: 99%

PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS

et al. 2013

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Section: Introductionmentioning

confidence: 99%

“…cGMP has different effects on inflammation under stimulated versus unstimulated conditions [ 28 ]. In unstimulated conditions, treatment with GC activators (e.g., NO donor, ANP) enhances expression of inflammatory mediators including NFκB activity and pro-inflammatory cytokines [ 28 , 29 , 30 , 31 , 32 ]. Whereas these cGMP modulating treatments attenuate inflammatory responses in LPS- or TNF-α-stimulated conditions [ 28 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of Inflammatory Cytokine Production in Human Monocytes by cGMP and IRAK3

Nguyen

Axell

Turek

et al. 2022

IJMS

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Interleukin-1 receptor-associated kinase-3 (IRAK3) is a critical checkpoint molecule of inflammatory responses in the innate immune system. The pseudokinase domain of IRAK3 contains a guanylate cyclase (GC) centre that generates small amounts of cyclic guanosine monophosphate (cGMP) associated with IRAK3 functions in inflammation. However, the mechanisms of IRAK3 actions are poorly understood. The effects of low cGMP levels on inflammation are unknown, therefore a dose–response effect of cGMP on inflammatory markers was assessed in THP-1 monocytes challenged with lipopolysaccharide (LPS). Sub-nanomolar concentrations of membrane permeable 8-Br-cGMP reduced LPS-induced NFκB activity, IL-6 and TNF-α cytokine levels. Pharmacologically upregulating cellular cGMP levels using a nitric oxide donor reduced cytokine secretion. Downregulating cellular cGMP using a soluble GC inhibitor increased cytokine levels. Knocking down IRAK3 in THP-1 cells revealed that unlike the wild type cells, 8-Br-cGMP did not suppress inflammatory responses. Complementation of IRAK3 knockdown cells with wild type IRAK3 suppressed cytokine production while complementation with an IRAK3 mutant at GC centre only partially restored this function. Together these findings indicate low levels of cGMP form a critical component in suppressing cytokine production and in mediating IRAK3 action, and this may be via a cGMP enriched nanodomain formed by IRAK3 itself.

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“…Guanylyl cyclase type A (GC-A) belongs to a family of particulate guanylyl cyclases (pGCs) which similarly to the soluble guanylyl cyclases (sGCs) catalyze synthesis of a common secondary messenger, namely cyclic GMP (cGMP), involved in many cellular processes (Pilz & Casteel, 2003;Potter et al, 2006). Although both forms of GCs produce the same secondary messenger, activation of each of them triggers different signaling pathways leading to different cellular effects (Zolle et al, 2000;Su et al, 2005;Mitkiewicz et al, 2011). This indicates that the final effect of cGMP depends on the site of its synthesis in the cell (cytosol or cell membrane).…”

Section: Introductionmentioning

confidence: 99%

“…Reports demonstrate anti-inflammatory action of this enzyme. It was found that the ANP-triggered GC-A/ cGMP-signaling pathway decreases activity of AP-1 and NF-κB transcription factors in activated myeloid cells and thus suppresses release of inflammatory cytokines (IL-1β, IL-6, TNFα) and inhibits expression of inducible nitric oxide synthase (Kiemer et al, 2000;Mitkiewicz et al, 2011;Mezzasoma et al, 2016). The anti-inflammatory action of ANP was shown to also occur in mice treated with LPS (Ladetzki-Baehs et al, 2007;Nojiri et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Sp1 mediates phorbol ester (PMA)-induced expression of membrane-bound guanylyl cyclase GC-A in human monocytic cells*

et al. 2018

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Cyclic guanosine monophosphate (cGMP) is synthesized by two types of enzymes: particulate (membrane-bound) guanylyl cyclases (pGCs) and soluble (cytosolic) guanylyl cyclases (sGCs). sGCs are primarily activated by binding of nitric oxide to their prosthetic heme group while pGCs are activated by binding of peptide ligands to their extracellular domains. One of them, pGC type A (GC-A) is activated by atrial and brain natriuretic peptides (ANP and BNP, respectively). Human monocytes isolated from peripheral blood mononuclear cells have been found to display sGC expression without concomitant expression of GC-A. However, GC-A activity appears in monocytes under certain conditions but a molecular mechanism of GC-A expression is still poorly understood. In this report we show that phorbol ester (PMA) induces transcription of a gene encoding GC-A in human monocytic THP-1 cells. Moreover, we find that PMA-treated THP-1 cells raise cGMP content following treatment with ANP. Studies using pharmacological inhibitors of protein kinases suggest involvement of protein kinase C (PKC), mitogen extracellular kinases (MEK1/2), and extracellular signal-regulated kinases (ERK1/2) in PMA-induced expression of the GC-A encoding gene in THP-1 cells. Finally, we show that PMA stimulates binding of Sp1 transcription factor to GC-rich DNA sequences and mithramycin A (a selective Sp1 inhibitor) inhibits expression of the GC-A mRNA in PMA-treated THP-1 cells. Taken together, our findings suggest that the PMA-stimulated PKC and MEK/ERK signaling pathways induce Sp1-mediated transcription of the GC-A encoding gene in human monocytic THP-1 cells.

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Different effects of soluble and particulate guanylyl cyclases on expression of inflammatory cytokines in rat peripheral blood mononuclear cells

Cited by 8 publications

References 44 publications

PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS

PDE5 inhibitors blunt inflammation in human BPH: A potential mechanism of action for PDE5 inhibitors in LUTS

Modulation of Inflammatory Cytokine Production in Human Monocytes by cGMP and IRAK3

Sp1 mediates phorbol ester (PMA)-induced expression of membrane-bound guanylyl cyclase GC-A in human monocytic cells*

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