Role of an indole-thiazolidiene PPAR pan ligand on actions elicited by G-protein coupled receptor activated neutrophils

Santin, José Roberto; Machado, Isabel Daufenback; Drewes, Carine Cristiane; Kupa, Léonard de Vinci Kanda; Soares, Rodrigo Marcondes; Cavalcanti, Danielle Maia de Holanda; Pitta, Ivan da Rocha; Farsky, Sandra Helena Poliselli

doi:10.1016/j.biopha.2018.06.056

Cited by 6 publications

(3 citation statements)

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“…When neutrophils are activated by cytokines, chemokines or other chemoattractants, a sequence of downstream events activate multiple phospholipases that act on membrane phospholipids [33]. Activation of the phosphoinositide-specific phospholipase Cβ then generates inositol triphosphate, which consequently initiates the mobilization of Ca 2+ from intracellular stores [33][34][35]. Typically, very rapid immobilization of intracellular Ca 2+ is the first indicator of cell activation [36].…”

Section: Discussionmentioning

confidence: 99%

Identification of N-formylated Peptides with Neutrophilic Chemotactic Activity in Mycobacterium tuberculosis

et al. 2022

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Neutrophil infiltration of the lungs is associated with granuloma formation and the severity of tuberculosis infection. Although several cytokines and chemokines are known to contribute to lung neutrophil infiltration, the neutrophilic chemotactic factors of Mycobacterium tuberculosis (Mtb) remain unexplored. Therefore, we performed Transwell based chemotactic assays using neutrophils from human peripheral blood and mouse bone marrow to probe the chemotactic activity of the culture filtrates (CF) of Mtb H37Rv. CF of H37Rv induced chemotaxis of both human and mouse neutrophils, and this was also confirmed with CF of 9 clinical isolates and Erdman strain of Mtb with neutrophil chemotactic activity. Sulfasalazine, an N-formyl-Met-Leu-Phe (fMLF) receptor inhibitor, blocked the chemotaxis of neutrophils induced by CF of Mtb, thus indicating the involvement of the fMLF receptor in Mtb CF induced chemotaxis of neutrophils. Mass spectrometry analysis of CF of H37Rv identified three candidate N-formylated heptapeptides. The chemotactic activity of the identified peptides was confirmed with their synthetic mimetics that they induced neutrophil chemotaxis in a manner dependent on N-terminal formylation. For all formylated peptides and CF of Mtb, the induced Ca2+ influx in neutrophils was suppressed by sulfasalazine. Thus, we identified novel formylated Mtb peptides with neutrophil chemotactic activity.

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Section: Discussionmentioning

confidence: 99%

Identification of N-formylated Peptides with Neutrophilic Chemotactic Activity in Mycobacterium tuberculosis

et al. 2022

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“…Neutrophils were obtained from the fluid leakage of the mouse peritoneal lavage, washed with PBS (pH 7.6), and the mixture was centrifuged at 900 × g for 10 min at 4°C (Sorvall™ ST 40, Thermo Scientific®, Swedesboro, NJ, USA). After washing, the neutrophils were suspended in PBS (pH 7.6) and 30 μ L of this cell suspension (1 × 10 6 ) was incubated with 10 μ L of different doses of noreugenin (NRG: 1, 2.5, 5, 10, 50, or 100 μ M) or α -hydroxy-butein (AH-BU: 1, 2.5, 5, 10, 50, or 100 μ M) in the presence or absence of lipopolysaccharide (LPS: 5 μ g/mL, 10 μ L) (LPS from Escherichia coli serotype O111:B4, Sigma-Aldrich, St. Louis, MO, USA), for 18 h in an enzyme immunoassay (EIE) plate [21–23]. For the next step, 10 μ L of neutrophil suspension from each sample of the different doses of the compounds was mixed with 10 μ L of trypan blue dye solution (0.4%).…”

Section: Methodsmentioning

confidence: 99%

Phenolic Compounds Isolated fromCalea unifloraLess. Promote Anti-Inflammatory and Antioxidant Effects in Mice Neutrophils (Ex Vivo) and in Mice Pleurisy Model (In Vivo)

Rosa

Nascimento

Parisotto

et al. 2019

Mediators of Inflammation

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The literature shows that phenolic compounds possess important antioxidant and anti-inflammatory activities; however, the mechanism underlying these effects is not elucidated yet. The genus Calea is used in folk medicine to treat rheumatism, respiratory diseases, and digestive problems. In this context, some phenolic compounds were isolated with high purity from Calea uniflora Less. and identified as noreugenin (NRG) and α-hydroxy-butein (AH-BU). The aim of this study was to analyze the effect of these compounds on cell viability, the activity of myeloperoxidase (MPO), and apoptosis of mouse neutrophils using ex vivo tests. Furthermore, the effect of these compounds on the cytokines, interleukin 1 beta (IL-1β), interleukin 17A (IL-17A), and interleukin 10 (IL-10), and oxidative stress was investigated by analyzing lipid peroxidation (the concentration of thiobarbituric acid reactive substances (TBARS)) and activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), using a murine model of neutrophilic inflammation. The NRG and AH-BU reduce MPO activity and increase neutrophil apoptosis (p < 0.05). These compounds reduced the generation of oxygen reactive species and IL-1β and IL-17A levels but increased IL-10 levels (p < 0.05). This study demonstrated that NRG and AH-BU show a significant anti-inflammatory effect by inhibiting the MPO activity and increasing neutrophil apoptosis in primary cultures of mouse neutrophils. These effects were at least partially associated with blocking reactive species generation, inhibiting IL-1β and IL-17A, and increasing IL-10 levels.

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“…Lyso-7 has a potent in vivo beneficial effect on inflammation and microcirculatory damage and the development of atherosclerotic lesions [ 13 ]. Lyso-7 exhibits anti-inflammatory effects via inhibition of expression of adhesion proteins, abolishing the adhesion of neutrophils to endothelial cells, and effects on blocking the enhancement of intracellular Ca 2+ levels in neutrophils [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

et al. 2021

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Lyso-7 is a novel synthetic thiazolidinedione, which is a receptor (pan) agonist of PPAR α,β/δ,γ with anti-inflammatory activity. We investigated the cardiotoxicity of free Lyso-7 in vitro (4.5–450 nM), and Lyso-7 loaded in polylactic acid nanocapsules (NC) in vivo (Lyso-7-NC, 1.6 mg/kg). In previous work, we characterized Lyso-7-NC. We administered intravenously Lyso-7, Lyso-7-NC, control, and blank-NC once a day for seven days in mice. We assessed cell contraction and intracellular Ca2+ transients on single mice cardiomyocytes enzymatically isolated. Lyso-7 reduced cell contraction and accelerated relaxation while lowering diastolic Ca2+ and reducing Ca2+ transient amplitude. Lyso-7 also promoted abnormal ectopic diastolic Ca2+ events, which isoproterenol dramatically enhanced. Incorporation of Lyso-7 in NC attenuated drug effects on cell contraction and prevented its impact on relaxation, diastolic Ca2+, Ca2+ transient amplitude, Ca2+ transient decay kinetics, and promotion of diastolic Ca2+ events. Acute effects of Lyso-7 on cardiomyocytes in vitro at high concentrations (450 nM) were globally similar to those observed after repeated administration in vivo. In conclusion, we show evidence for off-target effects of Lyso-7, seen during acute exposure of cardiomyocytes to high concentrations and after repeated treatment in mice. Nano-encapsulation of Lyso-7 in polymeric NC attenuated the unwanted effects, particularly ectopic Ca2+ events known to support life-threatening arrhythmias favored by stress or exercise.

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Role of an indole-thiazolidiene PPAR pan ligand on actions elicited by G-protein coupled receptor activated neutrophils

Cited by 6 publications

References 50 publications

Identification of N-formylated Peptides with Neutrophilic Chemotactic Activity in Mycobacterium tuberculosis

Identification of N-formylated Peptides with Neutrophilic Chemotactic Activity in Mycobacterium tuberculosis

Phenolic Compounds Isolated fromCalea unifloraLess. Promote Anti-Inflammatory and Antioxidant Effects in Mice Neutrophils (Ex Vivo) and in Mice Pleurisy Model (In Vivo)

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione

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