Limits...
Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model.

Stuqui B, de Paula-Silva M, Carlos CP, Ullah A, Arni RK, Gil CD, Oliani SM - PLoS ONE (2015)

Bottom Line: In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules.Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules.Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunomorphology, Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

ABSTRACT
Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II-induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV-induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1β and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

No MeSH data available.


Related in: MedlinePlus

Model to summarize the effects of Ac2-26 treatment after either CV or MjTX-II induced peritonitis.Local inflammation in the peritoneal exudate augments the number of neutrophils and the pro-inflammatory cytokines, IL-1β and IL-6 (A). This inflammation is decreased after Ac2-26 treatment (B). In the mesentery, the inflammatory response promotes the influx of macrophages, and increases the number of neutrophils, degranulated mast cells and the levels of AnxA1 expression (C). The Ac2-26 treatment decreased the numbers of all the inflammatory cells (D). The systemic inflammation results in an increase of neutrophils in the bloodstream (E); these levels are restored after Ac2-26 post-treatment (F). In the kidney (G), MjTX-II augmented the infiltration by macrophages (H) and Ac2-26 prevented this influx (I). Histopathological analysis showed direct (casts) and indirect (pyknotic nuclei/karyolysis) effects of the envenoming (J), which were restored by the Ac2-26 treatment (K). Higher levels of AnxA1 were observed in the distal tubules and glomerular cells after the administration of either CV or MjTX-II (L), and these levels decreased with the anti-inflammatory treatment (M).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492549&req=5

pone.0130803.g008: Model to summarize the effects of Ac2-26 treatment after either CV or MjTX-II induced peritonitis.Local inflammation in the peritoneal exudate augments the number of neutrophils and the pro-inflammatory cytokines, IL-1β and IL-6 (A). This inflammation is decreased after Ac2-26 treatment (B). In the mesentery, the inflammatory response promotes the influx of macrophages, and increases the number of neutrophils, degranulated mast cells and the levels of AnxA1 expression (C). The Ac2-26 treatment decreased the numbers of all the inflammatory cells (D). The systemic inflammation results in an increase of neutrophils in the bloodstream (E); these levels are restored after Ac2-26 post-treatment (F). In the kidney (G), MjTX-II augmented the infiltration by macrophages (H) and Ac2-26 prevented this influx (I). Histopathological analysis showed direct (casts) and indirect (pyknotic nuclei/karyolysis) effects of the envenoming (J), which were restored by the Ac2-26 treatment (K). Higher levels of AnxA1 were observed in the distal tubules and glomerular cells after the administration of either CV or MjTX-II (L), and these levels decreased with the anti-inflammatory treatment (M).

Mentions: The findings of this study are outlined in Fig 8 and, taken together, the data provides evidence that the N-terminal peptide of AnxA1, Ac2-26, significantly attenuated the local and systemic inflammatory processes. We propose that these experimental findings may have a significant impact on and relevance for the development of new therapeutic strategies for envenomation.


Ac2-26 Mimetic Peptide of Annexin A1 Inhibits Local and Systemic Inflammatory Processes Induced by Bothrops moojeni Venom and the Lys-49 Phospholipase A2 in a Rat Model.

Stuqui B, de Paula-Silva M, Carlos CP, Ullah A, Arni RK, Gil CD, Oliani SM - PLoS ONE (2015)

Model to summarize the effects of Ac2-26 treatment after either CV or MjTX-II induced peritonitis.Local inflammation in the peritoneal exudate augments the number of neutrophils and the pro-inflammatory cytokines, IL-1β and IL-6 (A). This inflammation is decreased after Ac2-26 treatment (B). In the mesentery, the inflammatory response promotes the influx of macrophages, and increases the number of neutrophils, degranulated mast cells and the levels of AnxA1 expression (C). The Ac2-26 treatment decreased the numbers of all the inflammatory cells (D). The systemic inflammation results in an increase of neutrophils in the bloodstream (E); these levels are restored after Ac2-26 post-treatment (F). In the kidney (G), MjTX-II augmented the infiltration by macrophages (H) and Ac2-26 prevented this influx (I). Histopathological analysis showed direct (casts) and indirect (pyknotic nuclei/karyolysis) effects of the envenoming (J), which were restored by the Ac2-26 treatment (K). Higher levels of AnxA1 were observed in the distal tubules and glomerular cells after the administration of either CV or MjTX-II (L), and these levels decreased with the anti-inflammatory treatment (M).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492549&req=5

pone.0130803.g008: Model to summarize the effects of Ac2-26 treatment after either CV or MjTX-II induced peritonitis.Local inflammation in the peritoneal exudate augments the number of neutrophils and the pro-inflammatory cytokines, IL-1β and IL-6 (A). This inflammation is decreased after Ac2-26 treatment (B). In the mesentery, the inflammatory response promotes the influx of macrophages, and increases the number of neutrophils, degranulated mast cells and the levels of AnxA1 expression (C). The Ac2-26 treatment decreased the numbers of all the inflammatory cells (D). The systemic inflammation results in an increase of neutrophils in the bloodstream (E); these levels are restored after Ac2-26 post-treatment (F). In the kidney (G), MjTX-II augmented the infiltration by macrophages (H) and Ac2-26 prevented this influx (I). Histopathological analysis showed direct (casts) and indirect (pyknotic nuclei/karyolysis) effects of the envenoming (J), which were restored by the Ac2-26 treatment (K). Higher levels of AnxA1 were observed in the distal tubules and glomerular cells after the administration of either CV or MjTX-II (L), and these levels decreased with the anti-inflammatory treatment (M).
Mentions: The findings of this study are outlined in Fig 8 and, taken together, the data provides evidence that the N-terminal peptide of AnxA1, Ac2-26, significantly attenuated the local and systemic inflammatory processes. We propose that these experimental findings may have a significant impact on and relevance for the development of new therapeutic strategies for envenomation.

Bottom Line: In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules.Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules.Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunomorphology, Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, São Paulo, Brazil.

ABSTRACT
Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein that modulates anti-inflammatory process and its therapeutic potential has recently been recognized in a range of systemic inflammatory disorders. The effect of the N-terminal peptide Ac2-26 of AnxA1 on the toxic activities of Bothrops moojeni crude venom (CV) and its myotoxin II (MjTX-II) were evaluated using a peritonitis rat model. Peritonitis was induced by the intraperitoneal injection of either CV or MjTX-II, a Lys-49 phospholipase A2. Fifteen minutes after the injection, the rats were treated with either Ac2-26 or PBS. Four hours later, the CV and MjTX-II-induced peritonitis were characterized by neutrophilia (in the peritoneal exudate, blood and mesentery) and increased number of mesenteric degranulated mast cells and macrophages. At 24 hours post-injection, the local inflammatory response was attenuated in the CV-induced peritonitis while the MjTX-II group exhibited neutrophilia (peritoneal exudates and blood). Ac2-26 treatment prevented the influx of neutrophils in MjTX-II-induced peritonitis and diminished the proportion of mesenteric degranulated mast cells and macrophages in CV-induced peritonitis. Additionally, CV and MjTX-II promoted increased levels of IL-1β and IL-6 in the peritoneal exudates which were significantly reduced after Ac2-26 treatment. At 4 and 24 hours, the endogenous expression of AnxA1 was upregulated in the mesenteric neutrophils (CV and MjTX-II groups) and mast cells (CV group). In the kidneys, CV and MjTX-II administrations were associated with an increased number of macrophages and morphological alterations in the juxtamedullary nephrons in proximal and distal tubules. Ac2-26 promoted significant recovery of the juxtamedullary structures, decreased the number of macrophages and diminished the AnxA1 in epithelial cells from distal tubules and renal capsules. Our results show that Ac2-26 treatment significantly attenuates local and systemic inflammatory processes and indicate this peptide as a potential target for the development of new therapeutic strategies for the snakebite envenomation treatment.

No MeSH data available.


Related in: MedlinePlus