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JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation of claudin-4.

Zheng Y, Zhang M, Zhao Y, Chen J, Li B, Cai W - Exp Ther Med (2014)

Bottom Line: Pulmonary edema, the expression of inflammatory cytokines and pathological alterations were found to be significantly attenuated in LPS-induced ALI following treatment with SP600125 in vivo.Furthermore, flow cytometric analysis demonstrated that the apoptotic rate was significantly reduced in a concentration-dependent manner following SP600125 injection.In combination, the results from the present study indicated that the JNK inhibitor SP600125 protected against LPS-induced ALI in vivo and in vitro, possibly by upregulating the expression of claudin-4.

View Article: PubMed Central - PubMed

Affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.

ABSTRACT
Although in vitro studies have previously demonstrated that mitogen-activated protein kinases are important for the activation of transcription factors and the regulation of proinflammatory mediators, the function of c-Jun NH2-terminal kinase (JNK) in acute lung injury (ALI) remains to be fully elucidated. The present study aimed to investigate the effect of the JNK selective inhibitor SP600125 on lipopolysaccharide (LPS)-induced ALI. Pulmonary edema, the expression of inflammatory cytokines and pathological alterations were found to be significantly attenuated in LPS-induced ALI following treatment with SP600125 in vivo. In vitro, it was demonstrated that SP600125 administration significantly improved A549 cell viability in a dose-dependent manner using the Cell Counting kit-8 and the 5-ethynyl-2'-deoxyuridine incorporation assay. Furthermore, flow cytometric analysis demonstrated that the apoptotic rate was significantly reduced in a concentration-dependent manner following SP600125 injection. At the molecular level, SP600125 treatment dose-dependently inhibited JNK activation and upregulated claudin-4 expression in vivo and in vitro. In combination, the results from the present study indicated that the JNK inhibitor SP600125 protected against LPS-induced ALI in vivo and in vitro, possibly by upregulating the expression of claudin-4.

No MeSH data available.


Related in: MedlinePlus

Effect of SP600125 administration on A549 cell viability and apoptosis. (A–C) Cells were treated with different concentrations of SP600125 (between 0 and 40 nM). The Cell Counting kit (CCK)-8 and EdU incorporation assay were then performed to measure the A549 cell viability. *P<0.05 vs. control; #P<0.05 vs. ALI. (D) A549 cells were treated with SP600125 and the apoptotic rate was detected using flow cytometry. *P<0.05 vs. control; #P<0.05 vs. ALI. ALI, acute lung injury; NS, normal saline; JNK, c-Jun NH2-terminal kinase; EdU, 5-ethynyl-2′-deoxyuridine.
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f2-etm-08-01-0153: Effect of SP600125 administration on A549 cell viability and apoptosis. (A–C) Cells were treated with different concentrations of SP600125 (between 0 and 40 nM). The Cell Counting kit (CCK)-8 and EdU incorporation assay were then performed to measure the A549 cell viability. *P<0.05 vs. control; #P<0.05 vs. ALI. (D) A549 cells were treated with SP600125 and the apoptotic rate was detected using flow cytometry. *P<0.05 vs. control; #P<0.05 vs. ALI. ALI, acute lung injury; NS, normal saline; JNK, c-Jun NH2-terminal kinase; EdU, 5-ethynyl-2′-deoxyuridine.

Mentions: The lung epithelial cell line A549 was used in the present study to investigate the effect of SP600125 on A549 cell viability and apoptosis. The results from the CCK-8 assay revealed that cell viability was significantly reduced following LPS treatment. By contrast, SP600125 administration significantly improved the viability of A549 cells in a dose-dependent manner (Fig. 2A). The results from the EdU assay were consistent with these results (Fig. 2B and C). Flow cytometry was used to determine the effect of SP600125 on cell apoptosis. The results demonstrated that SP600125 treatment significantly reduced the apoptotic rate of A549 cells in a dose-dependent manner (Fig. 2D). In combination, these results suggested that SP600125 was able to protect against LPS-induced ALI in rats in vitro.


JNK inhibitor SP600125 protects against lipopolysaccharide-induced acute lung injury via upregulation of claudin-4.

Zheng Y, Zhang M, Zhao Y, Chen J, Li B, Cai W - Exp Ther Med (2014)

Effect of SP600125 administration on A549 cell viability and apoptosis. (A–C) Cells were treated with different concentrations of SP600125 (between 0 and 40 nM). The Cell Counting kit (CCK)-8 and EdU incorporation assay were then performed to measure the A549 cell viability. *P<0.05 vs. control; #P<0.05 vs. ALI. (D) A549 cells were treated with SP600125 and the apoptotic rate was detected using flow cytometry. *P<0.05 vs. control; #P<0.05 vs. ALI. ALI, acute lung injury; NS, normal saline; JNK, c-Jun NH2-terminal kinase; EdU, 5-ethynyl-2′-deoxyuridine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061205&req=5

f2-etm-08-01-0153: Effect of SP600125 administration on A549 cell viability and apoptosis. (A–C) Cells were treated with different concentrations of SP600125 (between 0 and 40 nM). The Cell Counting kit (CCK)-8 and EdU incorporation assay were then performed to measure the A549 cell viability. *P<0.05 vs. control; #P<0.05 vs. ALI. (D) A549 cells were treated with SP600125 and the apoptotic rate was detected using flow cytometry. *P<0.05 vs. control; #P<0.05 vs. ALI. ALI, acute lung injury; NS, normal saline; JNK, c-Jun NH2-terminal kinase; EdU, 5-ethynyl-2′-deoxyuridine.
Mentions: The lung epithelial cell line A549 was used in the present study to investigate the effect of SP600125 on A549 cell viability and apoptosis. The results from the CCK-8 assay revealed that cell viability was significantly reduced following LPS treatment. By contrast, SP600125 administration significantly improved the viability of A549 cells in a dose-dependent manner (Fig. 2A). The results from the EdU assay were consistent with these results (Fig. 2B and C). Flow cytometry was used to determine the effect of SP600125 on cell apoptosis. The results demonstrated that SP600125 treatment significantly reduced the apoptotic rate of A549 cells in a dose-dependent manner (Fig. 2D). In combination, these results suggested that SP600125 was able to protect against LPS-induced ALI in rats in vitro.

Bottom Line: Pulmonary edema, the expression of inflammatory cytokines and pathological alterations were found to be significantly attenuated in LPS-induced ALI following treatment with SP600125 in vivo.Furthermore, flow cytometric analysis demonstrated that the apoptotic rate was significantly reduced in a concentration-dependent manner following SP600125 injection.In combination, the results from the present study indicated that the JNK inhibitor SP600125 protected against LPS-induced ALI in vivo and in vitro, possibly by upregulating the expression of claudin-4.

View Article: PubMed Central - PubMed

Affiliation: Department of Emergency, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.

ABSTRACT
Although in vitro studies have previously demonstrated that mitogen-activated protein kinases are important for the activation of transcription factors and the regulation of proinflammatory mediators, the function of c-Jun NH2-terminal kinase (JNK) in acute lung injury (ALI) remains to be fully elucidated. The present study aimed to investigate the effect of the JNK selective inhibitor SP600125 on lipopolysaccharide (LPS)-induced ALI. Pulmonary edema, the expression of inflammatory cytokines and pathological alterations were found to be significantly attenuated in LPS-induced ALI following treatment with SP600125 in vivo. In vitro, it was demonstrated that SP600125 administration significantly improved A549 cell viability in a dose-dependent manner using the Cell Counting kit-8 and the 5-ethynyl-2'-deoxyuridine incorporation assay. Furthermore, flow cytometric analysis demonstrated that the apoptotic rate was significantly reduced in a concentration-dependent manner following SP600125 injection. At the molecular level, SP600125 treatment dose-dependently inhibited JNK activation and upregulated claudin-4 expression in vivo and in vitro. In combination, the results from the present study indicated that the JNK inhibitor SP600125 protected against LPS-induced ALI in vivo and in vitro, possibly by upregulating the expression of claudin-4.

No MeSH data available.


Related in: MedlinePlus