Limits...
Resolvin D1 drives establishment of Leishmania amazonensis infection

View Article: PubMed Central - PubMed

ABSTRACT

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.

No MeSH data available.


Related in: MedlinePlus

Baicalein inhibits the L. amazonensis proliferation.The effect of 15-lipoxygenase in L. amazonensis intracellular growth was examined by treating infected macrophage cultures with indicated doses of Baicalein. (A) RvD1 levels were measured in culture supernatants 4 h post infection. (B) Counting viable parasites was assessed in cells treated with increasing doses of baicalein. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5385529&req=5

f6: Baicalein inhibits the L. amazonensis proliferation.The effect of 15-lipoxygenase in L. amazonensis intracellular growth was examined by treating infected macrophage cultures with indicated doses of Baicalein. (A) RvD1 levels were measured in culture supernatants 4 h post infection. (B) Counting viable parasites was assessed in cells treated with increasing doses of baicalein. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.

Mentions: To further delineate the direct link between intrinsic RvD1 induction and L. amazonensis replication, we treated infected macrophages with Baicalein, an inhibitor of 15-lipoxygenase16, which is a key enzyme involved in the production of RvD117. Treatment with Baicalein resulted in a dose dependent reduction of RvD1 production at 4 h post-infection (Fig. 6A). This reduction was associated with a significant decrease in intracellular parasite viability (Fig. 6B). These findings strongly argue that blocking RvD1 production may serve as a strategy to reduce intracellular L. amazonensis infection burden.


Resolvin D1 drives establishment of Leishmania amazonensis infection
Baicalein inhibits the L. amazonensis proliferation.The effect of 15-lipoxygenase in L. amazonensis intracellular growth was examined by treating infected macrophage cultures with indicated doses of Baicalein. (A) RvD1 levels were measured in culture supernatants 4 h post infection. (B) Counting viable parasites was assessed in cells treated with increasing doses of baicalein. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385529&req=5

f6: Baicalein inhibits the L. amazonensis proliferation.The effect of 15-lipoxygenase in L. amazonensis intracellular growth was examined by treating infected macrophage cultures with indicated doses of Baicalein. (A) RvD1 levels were measured in culture supernatants 4 h post infection. (B) Counting viable parasites was assessed in cells treated with increasing doses of baicalein. Data shown are mean and SE of one representative out two independent experiments. *P < 0.05, **P < 0.01.
Mentions: To further delineate the direct link between intrinsic RvD1 induction and L. amazonensis replication, we treated infected macrophages with Baicalein, an inhibitor of 15-lipoxygenase16, which is a key enzyme involved in the production of RvD117. Treatment with Baicalein resulted in a dose dependent reduction of RvD1 production at 4 h post-infection (Fig. 6A). This reduction was associated with a significant decrease in intracellular parasite viability (Fig. 6B). These findings strongly argue that blocking RvD1 production may serve as a strategy to reduce intracellular L. amazonensis infection burden.

View Article: PubMed Central - PubMed

ABSTRACT

Previous studies have indicated that the balance between different eicosanoids reflect the intensity of the inflammatory profile in patients with tegumentary leishmaniasis. More recently, pro-resolution lipid mediators have been shown to play critical roles in dampening pathological inflammatory processes to reestablish homeostasis in a diverse range of experimental settings. Among these lipid mediator, resolvins from D series have been described as potent anti-inflammatory and immunomodulatory mediators, and its activities include inhibition of leukocyte chemotaxis and blockage production of proinflammatory cytokines, while increasing the expression of regulatory mediators. Whether resolvins play significant roles in establishment and persistence of Leishmania infection is currently unknown. We addressed this question in the current study by assessing circulating levels of D-series resolvins in tegumentary leishmaniasis patients presenting with localized or diffuse disease. We found heightened expression of resolvin D1 in diffuse cutaneous leishmaniasis which was correlated with expression profile of biomarkers associated with disease pathogenesis. Additional in vitro experiments using primary human macrophages indicated that resolvin D1 may promote intracellular Leishmania amazonensis replication through a mechanism associated with induction of heme oxygenase-1. These results suggest that targeting resolvin D1 could serve as potential strategy for host directed therapy in diffuse cutaneous leishmaniasis.

No MeSH data available.


Related in: MedlinePlus