Journal
MOLECULAR IMMUNOLOGY
Volume 120, Issue -, Pages 13-22Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2020.01.014
Keywords
Dapk1; ALI; p38MAPK/NF-kappa B pathway; Autophagy; Inflammation; Oxidative stress
Categories
Funding
- China-Japan Friendship Hospital Foundation for Youth [2017-1-QN-7]
- National Science Foundation of China [81700260, 81774265]
Ask authors/readers for more resources
Objective: To investigate the impact of death-associated protein kinase 1 (Dapk1) on lipopolysaccharide (LPS)induced acute lung injury (ALI) via p38MAPK/NF-kappa B pathway. Methods: Dapk1(+/+) and Dapk1(-/-) mice were randomized into Control, LPS, SB203580 (a p38MAPK pathway inhibitor) + LPS, and PDTC (a NF-kappa B pathway inhibitor) + LPS groups. Cell counts, lung wet to dry weight ratio (W/D weight ratio), as well as indicators of oxidative stress were determined followed by the detection with HE staining, ELISA, qRT-PCR, Western blotting and Immunofluorescence. Besides, to explore whether the effect of Dapk1 on ALI directly mediated via p38MAPK/NF-kappa B pathway, mice were injected with TC-DAPK 6 (a Dapk1 inhibitor) with or without SB203580/PDTC before LPS administration. Results: LPS induced lung injury with increased lung W/D weight ratio, which could be partly reversed by SB203580 and PDTC in LPS-induced mice with activated p38MAPK/NF-kappa B pathway in lung tissues, especially in Dapk1(-/-) mice. SB203580 and PDTC reduced total cells and neutrophils in BALF in LPS-induced mice, accompanying with decreased levels of TNF-alpha, IL-6, MPO, LPO and MDA and the expressions of beclin-1, Atg5 and LC3II, but with the up-regulated activities of SOD and GSH-Px, as well as p62 protein expression. Besides, TC-DAPK 6 aggravated the pathologic injury in LPS-induced ALI with more serious inflammatory response, oxidative stress and autophagy as well as the activated p38MAPK/NF-kappa B pathway, which were reversed by SB203580 or PDTC. Conclusion: Dapk1 improved oxidative stress, inhibited autophagy, and reduce inflammatory response of LPS-induced ALI mice by inhibiting p38MAPK/NF-kappa B pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available