Recombinant Human Elafin Ameliorates Chronic Hyperoxia-Induced Lung Injury by Inhibiting Nuclear Factor-Kappa B Signaling in Neonatal Mice

Abstract

The study aimed to investigate whether recombinant human elafin can prevent hyperoxia-induced pulmonary inflammation in newborn mice, and to explore the mechanism underlying the inhibitory effects of elafin on nuclear factor-kappa B (NF-kB) signaling pathway. Neonatal C57BL/6J mice were exposed to 85% O 2 for 1, 3, 7, 14, or 21 days. Then, elafin was administered daily for 20 days through intraperitoneal injection. After treatment, morphometric analysis, quantitative real-time polymerase chain reaction, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and Western blotting were carried out to determine the key markers involved in inflammatory process and the potential signaling pathways in hyperoxia-exposed newborn mice treated with elafin. In neonatal bronchopulmonary dysplasia (BPD) mice, hyperoxia induced apoptosis by increasing Bcl-2-associated X protein expression, and triggered inflammation by upregulating the expression levels of interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor-a. Moreover, hyperoxia activated NF-kB signaling pathway by promoting the nuclear translocation of p65 in lung tissue. However, all these changes could be inhibited or reversed by elafin at least partially. Elafin reduced apoptosis, suppressed inflammation cytokines, and improved NF-kB p65 nuclear accumulation in hyperoxia-exposed neonatal mice, indicating that this recombinant protein can serve as a novel target for the treatment of BPD.

Psoralen inhibits the inflammatory response and mucus production in allergic rhinitis by inhibiting the activator protein 1 pathway and the downstream expression of cystatin‑SN

“…In the present study, the expression levels of IL-6 and IL-8 were detected in the cells to explore the effect of PSO on the inflammatory response in IL-13-induced JME/CF15 cells. The IL-6 and IL-8 proteins in the cell supernatant were very small and difficult to collect, so the expression of IL-6 and IL-8 in the cells was measured (32). The expression levels of IL-6 and IL-8 in cells have been detected in numerous previous studies, in which the expression of IL-6 and IL-8 in the cell supernatant was not detected (32)(33)(34).…”

Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants

“…These findings indicated that two peptides may play an antiinflammatory role in the process of BPD. And previous studies have shown that the regulation of inflammation-related signal pathways such as p38 mitogen activated protein kinases (p38MAPK) signal pathways and nuclear factor-κB (NF-κB) signal pathway can reduce the level of pro-inflammatory cytokines, thus relieving the pulmonary inflammation of BPD [ 76 , 77 ]. Combined with previous studies, we consider that the two peptides secreted from hUC-MSCs may decrease the production of pro-inflammatory cytokines through inflammation-related signal pathways and further researches need to be conducted to validate the possible pathway.…”

Peptidome Analysis of Umbilical Cord Mesenchymal Stem Cell (hUC-MSC) Conditioned Medium from Preterm and Term Infants

“…These ndings indicated that two peptides may play an anti-in ammatory role in the process of BPD. And previous studies have shown that the regulation of in ammation-related signal pathways such as p38 mitogen activated protein kinases (p38MAPK) signal pathways and nuclear factor-κB (NF-κB) signal pathway can reduce the level of pro-in ammatory cytokines, thus relieving the pulmonary in ammation of BPD [78,79].…”