Indoprofen exerts a potent therapeutic effect against sepsis by alleviating high mobility group box 1-mediated inflammatory responses
| Autor: | Jinyi Zhou, Juanjuan Liang, Xintong Yan, Shuai Lu, Baolin Jiang, Xiaowen Bi, Lan Luo, Jie Liu, Zhimin Yin |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Lipopolysaccharide THP-1 Cells Receptor for Advanced Glycation End Products Anti-Inflammatory Agents Pharmacology Toxicology HMGB1 Monocytes Proinflammatory cytokine Sepsis chemistry.chemical_compound Mice In vivo medicine Animals Humans Cyclooxygenase Inhibitors HMGB1 Protein Receptor Lung Mice Inbred BALB C biology business.industry Macrophages Indoprofen medicine.disease Toll-Like Receptor 2 Toll-Like Receptor 4 Disease Models Animal RAW 264.7 Cells chemistry biology.protein Cytokines Cyclooxygenase Inflammation Mediators business medicine.drug Signal Transduction |
| Zdroj: | Toxicology and applied pharmacology. 433 |
| ISSN: | 1096-0333 |
| Popis: | Indoprofen is a non-steroidal anti-inflammatory drug, and has provided insights into treatment of spinal muscular atrophies; however, the treatment effect of indoprofen on sepsis and the precise underlying mechanism remain to be elucidated. This study was carried out to examine the inhibitory effect of indoprofen on high mobility group box 1 (HMGB1)-mediated inflammatory responses in vivo and in vitro. Intraperitoneal injection of indoprofen (20 or 40 mg/kg) at 8 h post-sepsis markedly improved the survival of BALB/c mice and ameliorated multiple-organ injury by blocking the inflammatory responses. In addition, indoprofen partially reduced the HMGB1 level in the serum and in the lung, as well as ameliorated pulmonary edema. Mechanistically, indoprofen potently inhibited the release of HMGB1 following stimulation by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C), and suppressed recombinant human HMGB1(rhHMGB1)-induced inflammatory responses. It was also found that indoprofen has both cyclooxygenase 2-dependent and -independent inhibitory effects on the proinflammatory effect of HMGB1 in THP-1 cells. Further, the drug reduced rhHMGB1-induced cell surface levels of toll-like receptor 2, toll-like receptor 4, and receptor of advanced glycation end-products in a concentration-dependent manner. Collectively, these data demonstrated that the anti-inflammatory effect of indoprofen in sepsis was associated with HMGB1-mediated inflammatory responses, thus offering a favorable mechanistic basis to support the therapeutic potential of indoprofen for the treatment of lethal sepsis or other inflammatory diseases. |
| Databáze: | OpenAIRE |
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