Inhibition Of JNK Phosphorylation By Curcumin Analog C66 Protects LPS-Induced Acute Lung Injury

Abstract

Background

Acute lung injury (ALI) is characterized by high prevalence and high mortality. Thus far, no effective pharmacological treatment has been made for ALI in clinics. Inflammation is critical to the development of ALI. Curcumin analog C66, having reported as an inhibitor of c-Jun N-terminal kinase (JNK), exhibits anti-inflammatory property both in vitro and in vivo. However, whether C66 is capable of reducing lipopolysaccharide (LPS)-induced ALI through the inhibition of inflammation by targeting JNK remains unknown.

Methods

Intratracheal injection of LPS was employed to build a mouse ALI model. H&E staining, wet/dry ratio, immunofluorescence staining, inflammatory cell detection, and inflammatory gene expression were used to evaluate lung injury and lung inflammation. In vitro, LPS was used to induce the expression of inflammatory cytokines both in protein and gene levels.

Results

The results of our studies showed that the pretreatment with C66 and JNK inhibitor SP600125 was capable of attenuating the LPS-induced ALI by detecting pulmonary edema, pathological changes, total protein concentration, and inflammatory cell number in bronchoalveolar lavage fluid (BALF). Besides, C66 and SP600125 also suppressed LPS-induced inflammatory cytokine expression in BALF, serum, and lung tissue. In vitro, LPS-induced production of TNF-α and IL-6 and gene expression of TNF-α, IL-6, IL-1β, and COX-2 could be inhibited by the pretreatment with C66 and SP600125. It was found that C66 and SP600125 could inhibit LPS-induced phosphorylation of JNK both in vitro and in vivo.

Conclusion

In brief, our results suggested that C66 protects LPS-induced ALI through the inhibition of inflammation by targeting the JNK pathway. These findings further confirmed the pivotal role of JNK in ALI and implied that C66 is likely to serve as a potential therapeutic agent for ALI.

Keywords:

• acute lung injury
• lipopolysaccharide
• JNK
• C66
• inflammation

View correction statement:

Inhibition of JNK Phosphorylation by Curcumin Analog C66 Protects LPS-Induced Acute Lung Injury [Corrigendum]

Acknowledgment

The language of this manuscript has been revised by a native speaker from Zibo Yimore Translation Co. Ltd.

Abbreviations

ALI, acute lung injury; BALF, bronchoalveolar lavage fluid; LPS, lipopolysaccharide; JNK, c-Jun N-terminal Kinase; MAPKs, mitogen activated protein kinases; MPMs, mouse peritoneal macrophages; SEM, mean ± standard error of the mean.

Author Contributions

All authors contributed to data analysis, drafting, or revising the article; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare there are no competing interests.

Additional information

Funding

This study was supported by the Natural Science Funding of China (21572166 to Y.Z., and 81770850 to X.S.), Zhejiang Provincial Natural Science Funding (LY19H310002 to B.Z., and LY17H050007 to X.S.), and Project for Science and Technology of Huzhou (2015GY08 to L.G.).