Mechanism of IL‑8‑induced acute lung injury through pulmonary surfactant proteins A and B

Abstract

This study explored how interleukin-8 (IL-8) causes acute lung injury (ALI) through pulmonary surfactant protein A (SP-A) and surfactant protein B (SP-B). Serum was collected from 53 ALI patients and further 56 healthy subjects who underwent physical examination. The IL-8, SP-A, and SP-B levels were determined using enzyme-linked immunosorbent assay (ELISA). An ALI model was constructed using lipopolysaccharide (LSP)-induced normal A549 cells. siRNA was employed to interfere with the expression of IL-8, SP-A and SP-B. Western blot analysis was carried out to determine the protein levels, and MTT assay to determine the cell activity. In addition, co-immunoprecipitation (Co-IP) assay was used to verify the interaction between IL-8, SP-A and SP-B. ALI patients showed high expression of serum IL-8, and low expression of SP-A and SP-B, and IL-8 was negatively correlated with SP-A and SP-B, respectively. LSP-induced normal A549 cells showed increased expression of IL-8 and decreased expression of SP-A and SP-B. Silencing IL-8 led to increased expression levels of SP-A, SP-B and Bcl2, decreased expression levels of caspase-9, caspase-3, Bax, TNF-α, IL-17 and IL-1β, reduced cell apoptosis rate, and enhanced cell viability. Silencing SP-A and SP-B resulted in increased expression of IL-8, caspase-9, caspase-3, Bax, TNF-α, IL-17 and IL-1β, and decreased expression of Bcl2. Co-IP assay revealed that IL-8 could interact with SP-A and SP-B, respectively. IL-8 induces apoptosis by inhibiting SP-A and SP-B, and intensifies cellular inflammatory reaction, leading eventually to ALI.

Methane Inhalation Protects Against Lung Ischemia-Reperfusion Injury in Rats by Regulating Pulmonary Surfactant via the Nrf2 Pathway

“…Pulmonary surfactant consists of phospholipids and surfactant proteins ( Yang et al, 2020 ). Pulmonary surfactant can stabilize the alveoli at the end of exhalation and prevent collapse by maintaining alveolar surface tension ( Topercerova et al, 2019 ).…”

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“…Finally, the most important action of the described treatment is the anti-inflammatory one. Regarding this, changes in the structure and function of surfactant proteins, such as surfactant protein A (SP-A) and surfactant protein B (SP-B), increase the susceptibility to lung diseases: SP-A not only maintains the epithelial integrity by inhibiting lung cell apoptosis, but also controls inflammatory response by inhibiting inflammatory cytokines (TNF-α, IL-17 and IL-1β) [7].…”

Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway

“…SP-A is a member of the protein collectin family, characterized by a collagen-like region at the NH 2 end and a lectin domain at the COOH end. SP-A can regulate the lung immune response [30][31][32]. By combining with various pathogens, SP-A can enhance the absorption of pathogens by phagocytes [33].…”