scholarly journals Biological and Inflammatory Effects of Antigen 5 from Polybia paulista (Hymenoptera, Vespidae) Venom in Mouse Intraperitoneal Macrophages

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 850
Author(s):  
Murilo Luiz Bazon ◽  
Luis Gustavo Romani Fernandes ◽  
Isabela Oliveira Sandrini Assugeni ◽  
Lucas Machado Pinto ◽  
Patrícia Ucelli Simioni ◽  
...  
Keyword(s):  
Peritoneal Macrophages ◽  
In Vivo Studies ◽  
M2 Macrophage ◽  
No Production ◽  
Activated Macrophages ◽  
In Vitro Production ◽  
Polybia Paulista ◽  
Antigen 5

The social wasp Polybia paulista (Hymenoptera, Vespidae) is highly aggressive, being responsible for many medical occurrences. One of the most allergenic components of this venom is Antigen 5 (Poly p 5). The possible modulation of the in vitro immune response induced by antigen 5 from P. paulista venom, expressed recombinantly (rPoly p 5), on BALB/c mice peritoneal macrophages, activated or not with LPS, was assessed. Here, we analyzed cell viability changes, expression of the phosphorylated form of p65 NF-κB subunit, nitric oxide (NO), proinflammatory cytokines production, and co-stimulatory molecules (CD80, CD86). The results suggest that rPoly p 5 does not affect NO production nor the expression of co-stimulatory molecules in mouse peritoneal macrophages. On the other hand, rPoly p 5 induced an increase in IL-1β production in non-activated macrophages and a reduction in the production of TNF-α and MCP-1 cytokines in activated macrophages. rPoly p 5 decreased the in vitro production of the phosphorylated p65 NF-κB subunit in non-activated macrophages. These findings suggest an essential role of this allergen in the polarization of functional M2 macrophage phenotypes, when analyzed in previously activated macrophages. Further investigations, mainly in in vivo studies, should be conducted to elucidate Polybia paulista Ag5 biological role in the macrophage functional profile modulation.

scholarly journals Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages

2020 ◽  
Vol 17 (13) ◽  
pp. 4856
Author(s):  
Selma A. S. Kückelhaus ◽  
Daniela Sant’Ana de Aquino ◽  
Tatiana K. Borges ◽  
Daniel C. Moreira ◽  
Luciana de Magalhães Leite ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Leishmania Amazonensis ◽  
In Vivo Studies ◽  
Public Health Issue ◽  
Neglected Diseases ◽  
No Production ◽  
Tnf Α ◽  
Production Of Hydrogen

Leishmania protozoans are the causal agents of neglected diseases that represent an important public health issue worldwide. The growing occurrence of drug-resistant strains of Leishmania and severe side effects of available treatments represent an important challenge for the leishmaniases treatment. We have previously reported the leishmanicidal activity of phylloseptin-1 (PSN-1), a peptide found in the skin secretion of Phyllomedusa azurea (=Pithecopus azureus), against Leishmania amazonensis promastigotes. However, its impact on the amastigote form of L. amazonensis and its impact on infected macrophages are unknown. In this work, we evaluated the effects of PSN-1 on amastigotes of L. amazonensis inside macrophages infected in vitro. We assessed the production of hydrogen peroxide and nitric oxide, as well as the levels of inflammatory and immunomodulatory markers (TGF-β, TNF-α and IL-12), in infected and non-infected macrophages treated with PSN-1. Treatment with PSN-1 decreased the number of infected cells and the number of ingested amastigotes per cell when compared with the untreated cells. At 32 µM (64 µg/mL), PSN-1 reduced hydrogen peroxide levels in both infected and uninfected macrophages, whereas it had little effect on NO production or TGF-β release. The effect of PSN-1 on IL-12 and TNF-α secretion depended on its concentration, but, in general, their levels tended to increase as PSN-1 concentration increased. Further in vitro and in vivo studies are needed to clarify the mechanisms of action of PSN-1 and its interaction with the immune system aiming to develop pharmacological applications.

scholarly journals A Limulus Antilipopolysaccharide Factor-Derived Peptide Exhibits a New Immunological Activity with Potential Applicability in Infectious Diseases

2000 ◽  
Vol 7 (4) ◽  
pp. 669-675 ◽  
Author(s):  
Maribel G. Vallespi ◽  
Luis A. Glaria ◽  
Osvaldo Reyes ◽  
Hilda E. Garay ◽  
Joel Ferrero ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Cyclic Peptides ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Peritoneal Macrophages ◽  
Induced Response ◽  
No Production ◽  
Human Mononuclear Cells

ABSTRACT Previous studies have shown that cyclic peptides corresponding to residues 35 to 52 of the Limulus antilipopolysaccharide (anti-LPS) factor (LALF) bind and neutralize LPS-mediated in vitro and in vivo activities. Therapeutic approaches based on agents which bind and neutralize LPS activities are particularly attractive because these substances directly block the primary stimulus for the entire proinflammatory cytokine cascade. Here we describe new activities of the LALF31–52 peptide, other than its LPS binding ability. Surprisingly, supernatants from human mononuclear cells stimulated with the LALF peptide are able to induce in vitro antiviral effects on the Hep-2 cell line mediated by gamma interferon (IFN-γ) and IFN-α. Analysis of the effect of LALF31–52 on tumor necrosis factor (TNF) and nitric oxide (NO) production by LPS-stimulated peritoneal macrophages revealed that a pretreatment with the peptide decreased LPS-induced TNF production but did not affect NO generation. This indicates that the LALF peptide modifies the LPS-induced response. In a model in mice with peritoneal fulminating sepsis, LALF31–52 protected the mice when administered prophylactically, and this effect is related to reduced systemic TNF-α levels. This study demonstrates, for the first time, the anti-inflammatory properties of the LALF-derived peptide. These properties widen the spectrum of the therapeutic potential for this LALF-derived peptide and the molecules derived from it. These agents may be useful in the prophylaxis and therapy of viral and bacterial infectious diseases, as well as for septic shock.

scholarly journals 1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study

2020 ◽  
Vol 21 (18) ◽  
pp. 6839 ◽  
Author(s):  
Fernando Almeida-Souza ◽  
Verônica Diniz da Silva ◽  
Gabriel Xavier Silva ◽  
Noemi Nosomi Taniwaki ◽  
Daiana de Jesus Hardoim ◽  
...  
Keyword(s):  
In Silico ◽  
Peritoneal Macrophages ◽  
In Vivo Studies ◽  
Topical Formulation ◽  
Current Standard ◽  
Current Standard Treatment ◽  
Predictive Study ◽  
Leishmania Parasites

The current standard treatment for leishmaniasis has remained the same for over 100 years, despite inducing several adverse effects and increasing cases of resistance. In this study we evaluated the in vitro antileishmanial activity of 1,4-disubstituted-1,2,3 triazole compounds and carried out in silico predictive study of their pharmacokinetic and toxicity properties. Ten compounds were analyzed, with compound 6 notably presenting IC50: 14.64 ± 4.392 µM against promastigotes, IC50: 17.78 ± 3.257 µM against intracellular amastigotes, CC50: 547.88 ± 3.256 µM against BALB/c peritoneal macrophages, and 30.81-fold selectivity for the parasite over the cells. It also resulted in a remarkable decrease in all the parameters of in vitro infection. Ultrastructural analysis revealed lipid corpuscles, a nucleus with discontinuity of the nuclear membrane, a change in nuclear chromatin, and kinetoplast swelling with breakdown of the mitochondrial cristae and electron-density loss induced by 1,4-disubstituted-1,2,3-triazole treatment. In addition, compound 6 enhanced 2.3-fold the nitrite levels in the Leishmania-stimulated macrophages. In silico pharmacokinetic prediction of compound 6 revealed that it is not recommended for topical formulation cutaneous leishmaniasis treatment, however the other properties exhibited results that were similar or even better than miltefosine, making it a good candidate for further in vivo studies against Leishmania parasites.

Effect of Peganum Harmala Seeds Extract on Nitric Oxide in U937 Monocytes and Macrophages

2020 ◽  
Author(s):  
Nima Rahmati ◽  
Fatemeh Hajighasemi
Keyword(s):  
Nitric Oxide ◽  
Aqueous Extract ◽  
Calf Serum ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Peganum Harmala ◽  
Logarithmic Growth Phase ◽  
Anti Inflammatory

Background and Aims: Nitric oxide (NO) has an essential role in inflammation and has been related to pathogenesis and the progress of numerous inflammatory-based diseases, including some cancers. Peganum harmala (P. harmala) is a medicinal plant used for the treatment of numerous diseases such as several infections. Also, anti-inflammatory effects of P. harmala extracts and its derivatives (harmaline and harmine) by suppressing myeloperoxidase, NO, and other mediators have been demonstrated in vivo. In this study, the effect of P. harmala seeds aqueous extract on NO production in U937 monocytic cells and peritoneal macrophages has been evaluated in vitro. Materials and Methods: U937 and mice peritoneal macrophages were cultured in Roswell Park Memorial institute-1640 with 10% fetal calf serum. Then, the cells at the logarithmic growth phase were incubated with different concentrations of aqueous extract of P. harmala seeds (0.1-1 mg/ml) for 24 hours. Next, NO production was assessed by the Griess method in the culture medium. Results: P. harmala seeds aqueous extract did not significantly affect lipopolysaccharide-induced NO production in U937 cells and peritoneal macrophages after 24 hours incubation time compared with untreated control cells. Conclusion: These results suggest that the anti-inflammatory effects of P. harmala may be mediated through NO-independent mechanism(s). However, further studies are warranted to define the P. harmala aqueous extract impact on NO expression in other related normal and cancerous cells.

scholarly journals Src Is a Prime Target Inhibited by Celtis choseniana Methanol Extract in Its Anti-Inflammatory Action

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Han Gyung Kim ◽  
Subin Choi ◽  
Jongsung Lee ◽  
Yo Han Hong ◽  
Deok Jeong ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Inflammatory Responses ◽  
Peritoneal Macrophages ◽  
Inflammatory Activity ◽  
Poly I:C ◽  
Raw264.7 Cells ◽  
No Production ◽  
Anti Inflammatory

Celtis choseniana is the traditional plant used at Korea as a herbal medicine to ameliorate inflammatory responses. Although Celtis choseniana has been traditionally used as a herbal medicine at Korea, no systemic research has been conducted on its anti-inflammatory activity. Therefore, the present study explored an anti-inflammatory effect and its underlying molecular mechanism using Celtis choseniana methanol extract (Cc-ME) in macrophage-mediated inflammatory responses. In vitro anti-inflammatory activity of Cc-ME was evaluated using RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS), pam3CSK4 (Pam3), or poly(I:C). In vivo anti-inflammatory activity of Cc-ME was investigated using acute inflammatory disease mouse models, such as LPS-induced peritonitis and HCl/EtOH-induced gastritis. The molecular mechanism of Cc-ME-mediated anti-inflammatory activity was examined by Western blot analysis and immunoprecipitation using whole cell and nuclear fraction prepared from the LPS-stimulated RAW264.7 cells and HEK293 cells. Cc-ME inhibited NO production and mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and tumor necrosis factor-alpha (TNF-α) in the RAW264.7 cells and peritoneal macrophages induced by LPS, pam3, or poly(I:C) without cytotoxicity. High-performance liquid chromatography (HPLC) analysis showed that Cc-ME contained anti-inflammatory flavonoids quercetin, luteolin, and kaempferol. Among those, the content of luteolin, which showed an inhibitory effect on NO production, was highest. Cc-ME suppressed the NF-κB signaling pathway by targeting Src and interrupting molecular interactions between Src and p85, its downstream kinase. Moreover, Cc-ME ameliorated the morphological finding of peritonitis and gastritis in the mouse disease models. Therefore, these results suggest that Cc-ME exerted in vitro and in vivo anti-inflammatory activity in LPS-stimulated macrophages and mouse models of acute inflammatory diseases. This anti-inflammatory activity of Cc-ME was dominantly mediated by targeting Src in NF-κB signaling pathway during macrophage-mediated inflammatory responses.

scholarly journals Regulation of arachidonic acid metabolism by macrophage activation.

1982 ◽  
Vol 155 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
W A Scott ◽  
N A Pawlowski ◽  
H W Murray ◽  
M Andreach ◽  
J Zrike ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Macrophage Activation ◽  
Peritoneal Macrophages ◽  
Arachidonic Acid Metabolism ◽  
Prostaglandin Synthesis ◽  
Activated Macrophages ◽  
Synthetic Enzymes ◽  
Oxygenated Products

Levels of zymosan-induced arachidonic acid (20:4) metabolism by peritoneal macrophages elicited with inflammatory agents and resident macrophages were similar. Thyioglycollate (THIO)-elicited macrophages represented the exception; however, the diminished metabolism by these cells was reproduced by exposing resident cells to 5 mg/ml THIO broth in vitro. In contrast, reduced prostaglandin synthesis by macrophages from mice variously treated with the immunologic agents, Corynebacterium parvum or Bacille Calmette Guérin (BCG), closely correlated with enhanced antitoxoplasma activity, one measure of macrophage activation. This relationship, although not causative, suggested that the capacity for 20:4 metabolism is a function of the macrophage activation state. Modulation of macrophage 20:4 metabolism in vivo apparently required factors in addition to lymphocyte-derived products. Treatment of resident macrophages in vitro with BCG lymphokine was without effect on 20:4 release or prostaglandin synthesis. Activated macrophages from animals inoculated i.p. with C. parvum exhibited reduced 20:4 release and also failed to metabolize 70% of the 20:4 released in response to a zymosan stimulus. Consequently, the quantities of 20:4 metabolites formed were significantly less than expected from 20:4 release. These activated macrophages displayed greatly reduced synthesis of prostacylcin and leukotriene C compared with other 20:4 metabolites. It appeared that factors that regulate macrophage 20:4 metabolism influence the level of the inducible phospholipase and synthetic enzymes for specific 20:4 oxygenated products.

The mmu_circ_0000335 inhibits M1 microglial-induced hippocampal neuronal apoptosis via the miR-19b-3p/SOCS1 axis in a mouse epilepsy model

2019 ◽  
Author(s):  
Yong Zhu ◽  
Qiong Li ◽  
Weiping Kuang ◽  
Jun Lu ◽  
Qin Wang ◽  
...  
Keyword(s):  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Cytokine Signaling ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Bioinformatics Analyses ◽  
M1 Macrophage

Abstract Background : Increasing evidence has demonstrated that circular RNAs (circRNAs) participate in epileptogenesis, but the expression profile and role of circRNAs in epilepsy remain unknown. A circRNA microarray was performed to examine epilepsy-related circRNAs. Bioinformatics analyses, luciferin reporter experiments and real-time quantitative PCR (Rt-qPCR) in vitro experiments were performed to demonstrate the mechanism of circRNA-mediated gene regulation of the microglial phenotype under epileptic conditions. Then, to further confirm the effect of circRNAs on nerve damage in the hippocampus, a mouse model of epilepsy was established by intraperitoneal injection of lithium chloride and pilocarpine. Results: The data indicated that 364 circRNAs were differentially expressed comparing epilepsy and control tissues. In particular, mmu_circ_0000335 expression was significantly downregulated in epileptic mice which was confirmed by Rt-qPCR. Overexpression of mmu_circ_0000335 promoted BV2 cell transformation into the M2 macrophage phenotype by increasing expression of CD206, Arg1, Ym1 and IL-10 while decreasing M1 macrophage markers IL-1β, IL-6, TNF-α and IFN-γ expressions under epileptic conditions. mmu_circ_0000335 expression triggered upregulation of Suppressor of Cytokine Signaling 1 (SOCS1) by decreasing miR-19b-3p levels, as determined by luciferase reporter assay. In vivo studies found that mmu_circ_0000335 overexpression decreased epilepsy-induced neural cell apoptosis in the hippocampus by reducing inflammatory cytokine expression. Immunofluorescence detection showed that mmu_circ_0000335 overexpression promoted microglial transformation into the M2 phenotype which had an anti-inflammatory effect. Conclusions: These results collectively indicated that mmu_circ_0000335 was involved in epilepsy progression by functioning as a miR-19b-3p sponge to enhance SOCS1 expression. Thus, mmu_circ_0000335 may be a candidate therapeutic target for epilepsy patients.

Impaired aldosterone production by long-term infusion of atrial natriuretic factor

1990 ◽  
Vol 258 (1) ◽  
pp. E51-E56
Author(s):  
M. Nagano ◽  
E. L. Bravo
Keyword(s):  
Angiotensin Ii ◽  
Atrial Natriuretic Factor ◽  
Plasma Concentrations ◽  
In Vivo Studies ◽  
In Vitro Production ◽  
Natriuretic Factor ◽  
Pressor Responses ◽  
Atrial Natriuretic

This study assessed the effect of chronic infusions of atrial natriuretic factor (ANF) on in vivo and in vitro production of aldosterone. Vehicle (saline) or rat ANF-(99-126) was intravenously infused at 100 ng.kg-1.h-1 for 5 consecutive days into male New Zealand White rabbits. At 5 days plasma ANF was 18 +/- 4.1 pg/ml in vehicle-infused and 48.5 +/- 9.0 in ANF-infused rabbits (P less than 0.01). Plasma renin activity was significantly less in ANF-infused rabbits (2.99 +/- 0.35 vs. 0.77 +/- 0.12 ng.ml-1.h-1, P less than 0.01); however no differences were observed in the basal plasma concentrations of aldosterone, corticosterone, potassium, or hematocrit. In in vivo studies, chronically administered ANF attenuated plasma aldosterone, but not pressor, responses to acutely infused angiotensin II given at doses of 4, 16, and 64 ng.kg-1.min-1 for 20 min each. In in vitro experiments, collagenase-dispersed adrenal capsular cells from ANF-infused rabbits exhibited significantly reduced maximal responses to adrenocorticotropic hormone, angiotensin II, and potassium. These results suggest that chronic small increases in circulating ANF can blunt selectively adrenocortical responses to aldosterone secretagogues without affecting pressor responses to angiotensin II.

scholarly journals Chemical Composition, Antimicrobial and Antiparasitic Screening of the Essential Oil from Phania matricarioides (Spreng.) Griseb.

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1615 ◽  
Author(s):  
Yamilet Gutiérrez ◽  
Ramón Scull ◽  
Anabel Villa ◽  
Prabodh Satyal ◽  
Paul Cos ◽  
...  
Keyword(s):  
Fungal Growth ◽  
Chemical Characterization ◽  
Peritoneal Macrophages ◽  
In Vivo Studies ◽  
Parasitic Protozoa ◽  
Reference Drug ◽  
Ic50 Values

Essential oils (EOs) have gained increasing attention due to their pharmacological effectiveness, and they also constitute some of the most popular natural products. In this study, we present the chemical characterization of the EO from Phania matricarioides and the in vitro activity/selectivity against a wide panel of bacteria, fungi and parasitic protozoa. Forty-five compounds were identified in the studied EO, of which lavandulyl acetate (40.1%) and thymyl isobutyrate (13.9%) were the major components. The EO did not inhibit bacterial or fungal growth at the maximum concentration tested (64 µg/mL), although it displayed activity on all evaluated protozoa (IC50 values ranging from 2.2 to 56.6 µg/mL). In parallel, the EO demonstrated a noteworthy cytotoxic activity against peritoneal macrophages (CC50 values of 28.0 µg/mL). The most sensitive microorganism was Trypanosoma cruzi, which had a superior activity (IC50 = 2.2 µg/mL) and selectivity (SI = 13) in respect to other parasitic protozoa and the reference drug (p < 0.05). Further in vivo studies are needed to evaluate the potential use of this EO and the main compounds as antitrypanosomal agents. To our knowledge, this is the first report of chemical characterization and antimicrobial assessment of the EO from P. matricarioides.

scholarly journals Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1519
Author(s):  
Yosuke Ono ◽  
Takako Kawakita ◽  
Osamu Yoshino ◽  
Erina Sato ◽  
Kuniyuki Kano ◽  
...  
Keyword(s):  
Peritoneal Fluid ◽  
Inflammatory Mediator ◽  
Peritoneal Macrophages ◽  
M2 Macrophage ◽  
Menstrual Phase ◽  
Sphingosine 1 Phosphate ◽  
Cox 2 ◽  
Dominant Condition

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis.

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