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Prognosis of sepsis induced by cecal ligation and puncture in mice improved by anti-Clonorchis Sinensis cyclopholin a antibodies.

Song T, Yang M, Chen J, Huang L, Yin H, He T, Huang H, Hu X - Parasit Vectors (2015)

Bottom Line: Lung and mesentery tissues were stained with hematoxylin-eosin.Anti-CsCyPA antibodies could combine with MuCyPA and inhibit its peptidyl prolyl isomerase (PPIase) activity.Furthermore, the survival rate was elevated, ranging from 10.0 % to 45.0 % compared to the control group.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. songtianzhang@163.com.

ABSTRACT

Background: Cyclophilin A (CyPA), a ubiquitously distributed intracellular protein, is thought to be one of the important inflammatory factors and plays a significant role in the development process of sepsis. In the form of cytokine, CyPA deteriorates sepsis by promoting intercellular communication, apoptosis of endothelial cells and chemotactic effect on inflammatory cells. In our previous study, cyclophilin A of Clonorchis sinensis (CsCyPA), a type of excretory-secretory antigen, could induce the patients infected with Clonorchis sinensis to produce specific anti-CsCyPA antibodies. In this study, we investigated whether anti-CsCyPA antibodies could cross-react with CyPA and then play a protective role against sepsis, just like other anti-cytokine antagonists.

Methods: The mice model with sepsis was established with cecal ligation and puncture (CLP). Fifty mg/kg purified anti-CsCyPA antibodies were injected via the caudal vein 6 h after the CLP operation, and persistent observation was performed for 72 h. Blood samples and tissues were collected at 6 h, 12 h, 24 h, 48 h and 72 h after CLP. Cytokines in serum were measured by ELISA. Lung and mesentery tissues were stained with hematoxylin-eosin. Endothelial cells (ECs) isolated from murine aorta were co-cultured with CyPA of mice (MuCyPA) and anti-CsCyPAs for 24 h, then, viability was measured by Cell Counting Kit-8.

Results: Anti-CsCyPA antibodies could combine with MuCyPA and inhibit its peptidyl prolyl isomerase (PPIase) activity. In the antibodies treatment group, blood coagulation indicators including PT, aPTT, D-dimer and platelet count were obviously more ameliorative, the proinflammary factors like IL-6, TNF-α, IL-1β were significantly lower at 12 h and 24 h after surgery and the viability of ECs was significantly improved compared to those in the control group. Furthermore, the survival rate was elevated, ranging from 10.0 % to 45.0 % compared to the control group.

Conclusions: These antibodies may have a favorable effect on sepsis via inhibition of enzymic activity or protection of endothelial cells.

No MeSH data available.


Related in: MedlinePlus

Change of Serum Cytokines in Mice after CLP. a  TNF-α concentration in mice serum; b IL-6 concentration in mice serum; c IL-1βconcentration in mice serum; d IL-4 concentration in mice serum; e IL-10 concentration in mice serum; f IFN-γ concentration in mice serum; *P < 0.05 versus CLP treatment group; **P < 0.01 versus CLP treatment group; ***P < 0.001 versus CLP treatment group
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Fig6: Change of Serum Cytokines in Mice after CLP. a  TNF-α concentration in mice serum; b IL-6 concentration in mice serum; c IL-1βconcentration in mice serum; d IL-4 concentration in mice serum; e IL-10 concentration in mice serum; f IFN-γ concentration in mice serum; *P < 0.05 versus CLP treatment group; **P < 0.01 versus CLP treatment group; ***P < 0.001 versus CLP treatment group

Mentions: Cytokines which promoted inflammation like TNF-α, IL-6 and adjusted inflammation like IL-4, IL-10 and IFN-γ were chosen to represent the systematic inflammation level. Administration of antibodies significantly reduced the levels of TNF-α, IL-6 and IL-1β in serum compared with CLP control mice (Fig 6a, b, c) at 12 h and 24 h after CLP. Adjustment Cytokine had no statistical meaning (Fig 6d, e, f).Fig 6


Prognosis of sepsis induced by cecal ligation and puncture in mice improved by anti-Clonorchis Sinensis cyclopholin a antibodies.

Song T, Yang M, Chen J, Huang L, Yin H, He T, Huang H, Hu X - Parasit Vectors (2015)

Change of Serum Cytokines in Mice after CLP. a  TNF-α concentration in mice serum; b IL-6 concentration in mice serum; c IL-1βconcentration in mice serum; d IL-4 concentration in mice serum; e IL-10 concentration in mice serum; f IFN-γ concentration in mice serum; *P < 0.05 versus CLP treatment group; **P < 0.01 versus CLP treatment group; ***P < 0.001 versus CLP treatment group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591565&req=5

Fig6: Change of Serum Cytokines in Mice after CLP. a  TNF-α concentration in mice serum; b IL-6 concentration in mice serum; c IL-1βconcentration in mice serum; d IL-4 concentration in mice serum; e IL-10 concentration in mice serum; f IFN-γ concentration in mice serum; *P < 0.05 versus CLP treatment group; **P < 0.01 versus CLP treatment group; ***P < 0.001 versus CLP treatment group
Mentions: Cytokines which promoted inflammation like TNF-α, IL-6 and adjusted inflammation like IL-4, IL-10 and IFN-γ were chosen to represent the systematic inflammation level. Administration of antibodies significantly reduced the levels of TNF-α, IL-6 and IL-1β in serum compared with CLP control mice (Fig 6a, b, c) at 12 h and 24 h after CLP. Adjustment Cytokine had no statistical meaning (Fig 6d, e, f).Fig 6

Bottom Line: Lung and mesentery tissues were stained with hematoxylin-eosin.Anti-CsCyPA antibodies could combine with MuCyPA and inhibit its peptidyl prolyl isomerase (PPIase) activity.Furthermore, the survival rate was elevated, ranging from 10.0 % to 45.0 % compared to the control group.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. songtianzhang@163.com.

ABSTRACT

Background: Cyclophilin A (CyPA), a ubiquitously distributed intracellular protein, is thought to be one of the important inflammatory factors and plays a significant role in the development process of sepsis. In the form of cytokine, CyPA deteriorates sepsis by promoting intercellular communication, apoptosis of endothelial cells and chemotactic effect on inflammatory cells. In our previous study, cyclophilin A of Clonorchis sinensis (CsCyPA), a type of excretory-secretory antigen, could induce the patients infected with Clonorchis sinensis to produce specific anti-CsCyPA antibodies. In this study, we investigated whether anti-CsCyPA antibodies could cross-react with CyPA and then play a protective role against sepsis, just like other anti-cytokine antagonists.

Methods: The mice model with sepsis was established with cecal ligation and puncture (CLP). Fifty mg/kg purified anti-CsCyPA antibodies were injected via the caudal vein 6 h after the CLP operation, and persistent observation was performed for 72 h. Blood samples and tissues were collected at 6 h, 12 h, 24 h, 48 h and 72 h after CLP. Cytokines in serum were measured by ELISA. Lung and mesentery tissues were stained with hematoxylin-eosin. Endothelial cells (ECs) isolated from murine aorta were co-cultured with CyPA of mice (MuCyPA) and anti-CsCyPAs for 24 h, then, viability was measured by Cell Counting Kit-8.

Results: Anti-CsCyPA antibodies could combine with MuCyPA and inhibit its peptidyl prolyl isomerase (PPIase) activity. In the antibodies treatment group, blood coagulation indicators including PT, aPTT, D-dimer and platelet count were obviously more ameliorative, the proinflammary factors like IL-6, TNF-α, IL-1β were significantly lower at 12 h and 24 h after surgery and the viability of ECs was significantly improved compared to those in the control group. Furthermore, the survival rate was elevated, ranging from 10.0 % to 45.0 % compared to the control group.

Conclusions: These antibodies may have a favorable effect on sepsis via inhibition of enzymic activity or protection of endothelial cells.

No MeSH data available.


Related in: MedlinePlus