Cytokine profile and nitric oxide levels in macrophages exposed to Leishmania infantum FML

Salehi, Reza; Ahmadabad, Hasan Namdar; Maryam, Nezafat Firizi; Fahimeh, BakhshiJoibari; Ghahremani, Amirali; Hatam, Gholamreza; Amin, Ghatee Mohammad

doi:10.1016/j.exppara.2019.05.004

Cited by 15 publications

(3 citation statements)

References 29 publications

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“…The culture supernatants from those infected and non-infected were evaluated for the stable end-product of reactive nitrogen species (NO, nitrates, and nitrites) using the Griess reaction, according to the Cayman Chemical instruction manual (Cayman Chemical, Ann Arbor, MI, USA). The nitrite level was determined by measuring the absorbance at a wavelength of 540 nm using a microplate reader (BioTek-ELx800) [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum

et al. 2023

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Leishmaniasis is a neglected tropical infectious disease with thousands of cases annually; it is of great concern to global health, particularly the most severe form, visceral leishmaniasis. Visceral leishmaniasis treatments are minimal and have severe adverse effects. As guanidine-bearing compounds have shown antimicrobial activity, we analyzed the cytotoxic effects of several guanidine-bearing compounds on Leishmania infantum in their promastigote and amastigote forms in vitro, their cytotoxicity in human cells, and their impact on reactive nitrogen species production. LQOFG-2, LQOFG-6, and LQOFG-7 had IC50 values of 12.7, 24.4, and 23.6 µM, respectively, in promastigotes. These compounds exhibited cytotoxicity in axenic amastigotes at 26.1, 21.1, and 18.6 µM, respectively. The compounds showed no apparent cytotoxicity in cells from healthy donors. To identify mechanisms of action, we evaluated cell death processes by annexin V and propidium iodide staining and nitrite production. Guanidine-containing compounds caused a significant percentage of death by apoptosis in amastigotes. Independent of L. infantum infection, LQOFG-7 increased nitrite production in peripheral blood mononuclear cells, which suggests a potential mechanism of action for this compound. Therefore, these data suggest that guanidine derivatives are potential anti-microbial molecules, and further research is needed to fully understand their mechanism of action, especially in anti-leishmanial studies.

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Section: Methodsmentioning

confidence: 99%

Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum

et al. 2023

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“…We observed SLs transfected with the miR-148a inhibitor there was more significant NO production, in contrast miR-148a mimic also decrease iNOS in SL in CanL ( Rebech et al, 2023 ), and similar study observed that overexpression of miR-148a in peripheral blood cells of rats was associated with low iNOS ( Yin et al, 2021 ). NO production by macrophages participates in the elimination of L. infantum and can be involved in Th1-type immune responses ( Reza et al, 2019 ). These findings suggest that miR-148a participates in NO regulation and that L. infantum could use miR-148a expression to favor its survival.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis

et al. 2023

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Canine Visceral leishmaniasis (CanL) poses a severe public health threat in several countries. Disease progression depends on the degree of immune response suppression. MicroRNAs (miRs) modulate mRNA translation into proteins and regulate various cellular functions and pathways associated with immune responses. MiR-21 and miR-148a can alter the parasite load and M1 macrophages are the principal cells in dogs’ leishmanicidal activity. A previous study found increased miR-21 and miR-148a in splenic leukocytes (SL) of dogs with CanL using microarray analysis and in silico analysis identified PTEN pathway targets. PTEN is involved in the immune regulation of macrophages. We measured PTEN and the production of reactive oxygen species (ROS) and nitric oxide (NO) before and after transfection SLs of dogs with CanL with mimic and inhibition of miR-21 and miR-148a. PTEN levels increased, NO and ROS decreased in SLs from dogs with CanL. Inhibition of miRNA-21 resulted in PTEN increase; in contrast, PTEN decreased after miR-148a inhibition. Nitrite (NO2) levels increased after transfection with miR-21 inhibitor but were decreased with miR-148a inhibitor. The increase in miR-21 promoted a reduction in ROS and NO levels, but miR-148a inhibition increased NO and reduced ROS. These findings suggest that miR-21 and miR-148a can participate in immune response in CanL, affecting PTEN, NO, and ROS levels.

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“…After the parasite enters the host, dendritic cells are activated, and the immune system changes with respect to Th1 response and IFN-γ production increases by stimulating the interleukin 12(IL-12) production. Studies have shown that M1 macrophages are stimulated to produce the nitric oxide (NO) by the inducible nitric oxide synthase (iNOS) and kill the parasites by increasing the level of IFN-γ against the parasite (33,34). Also, an increase in the IFN-γ level can lead to activation of Tc, natural killer (NK), and opsonin antibodies, such as IgG2a (35).…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

Rabienia

Roudbari

Ghanbariasad

et al. 2020

Preprint

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Background: Nowadays, the prevention of parasitic diseases including leishmaniasis is one of the health concerns in the world, and cutaneous leishmaniasis is the most common type of these diseases. So far, no drug or vaccine has been approved for definitive treatment of this disease.Methods: In this study, the recombinant lentiviral vaccine containing a new multi-epitope of KMP11 and HASPB of the Leishmania major (L. major) was synthesized that had previously been designed in-silico. The designed multi-epitope was subcloned into the pCDH513 lentiviral vector, and the recombinant lentiviral multi-epitope vaccine (rLV-multi-epitope) was synthesized in the HEK293T cell by the packaging vectors. Also, the Western Blotting method was used to confirm the gene expression. Then, the rLV-multi-epitope vaccine was injected twice, along with two control groups, PBS, and rLV-empty to immunize the BALB /c mice. Twenty-one days after the second injection, the splenocytes of the mice were isolated and stimulated with the Leishmania lysate.Results: The results of the enzyme-linked immunoassay (ELISA) test not only showed the titer of IFN-γ and IL-4 was increased in the immunized group compared to the controls, but also indicated that the ratio of IFN-γ to IL-4 cytokines in the main group was increased significantly. As a result, the Th1 response was generated in the main group. Moreover, the humoral immune response was assessed and the results showed that the ratio of IgG2a to IgG1 antibody in the sera of the immunized mice was increased compared to the control groups. Also, the ratio of IgG2a to IgG1 was increased in the main group. Therefore, the humoral immune response was increased, which can also have a positive effect on increasing the Th1 response.Conclusions: Our results showed that immunization by the new rLV-multi-epitope vaccine could stimulate the immune system towards the Th1 through increasing the IFN-γ production.

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Cytokine profile and nitric oxide levels in macrophages exposed to Leishmania infantum FML

Cited by 15 publications

References 29 publications

Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum

Leishmanicidal Activity of Guanidine Derivatives against Leishmania infantum

MicroRNA-21 and microRNA-148a affects PTEN, NO and ROS in canine leishmaniasis

Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

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