Minocycline attenuates oxidative and inflammatory injury in a intestinal perforation induced septic lung injury model via down-regulating lncRNA MALAT1 expression.

Abstract

BACKGROUND:

Oxidative stress and inflammatory responses play an important role in acute lung injury (ALI). Although minocycline (MINO) has anti-inflammatory effects and is a promising candidate in treating inflammatory diseases, the effect of MINO on ALI during sepsis is still unclear.

METHODS:

In the present study, a mouse model with intestinal perforation was established. C57BL/6 mice received cecal ligation and puncture (CLP) to induce sepsis-associated ALI. MINO was used to treat the mice via intraperitoneal injection at different doses (negative control, 20 mg/kg, 50 mg/kg and 100 mg/kg, respectively) 24 h after CLP. The severity of lung injury was evaluated by pathological examination, and lung wet / dry weight ratio was calculated to evaluate the severity of pulmonary edema. The changes of TNF-α, IL-1β, IL-6, PGE2, MDA, NF-κB, Nrf2, Keap1 and lncRNA MALAT1 levels in lung tissues of the mice were detected with ELISA, chemical colorimetry, Western blot or qRT-PCR.

RESULTS:

MINO ameliorated the lung edema and lung injury of the mice induced by CLP in a dose-dependent manner. MINO administration could significantly down-regulate expressions of TNF-α, IL-6, IL-1β, PGE2 and MDA in lung tissues of the mice. Mechanistically, MINO exerted the effects of anti-inflammation and anti-oxidative stress through down-regulating the expression of MALAT1 and regulating Nrf2/Keap1 and NF-κB signaling pathways.

CONCLUSION:

MINO represses oxidative stress and inflammatory response during sepsis-induced ALI via down-regulating MALAT1 expression, and it has the potential to treat septic ALI.

• Authors: Ning Cui, Yong Liang, Junyu Wang, Bo Liu, Bing Wei, Yu Zhao
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 100 Pg. 108115 (Nov 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 34562841 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Interleukins
• Kelch-Like ECH-Associated Protein 1
• Malat1 long non-coding RNA, mouse
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• RNA, Long Noncoding
• Tumor Necrosis Factor-alpha
• Malondialdehyde
• Minocycline
• Dinoprostone

Topics

• Acute Lung Injury (drug therapy)
• Animals
• Dinoprostone
• Interleukins (metabolism)
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Lung (pathology)
• Male
• Malondialdehyde (metabolism)
• Mice
• Mice, Inbred C57BL
• Minocycline (pharmacology)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• RNA, Long Noncoding (metabolism)
• Sepsis (drug therapy)
• Tumor Necrosis Factor-alpha (metabolism)