Abstract
In this study, the effects of single immunoglobin IL-1 receptor-related protein (SIGIRR) on tumor necrosis factor- (TNF-) receptor-associated factor 6 (TRAF6) ubiquitination in acute lung injury (ALI) were evaluated in both alveolar epithelial cells and alveolar macrophage cells in vitro. Our results found that SIGIRR negatively regulated TRAF6 ubiquitination and such SIGIRR inhibition could enhance the TRAF6 expression in both alveolar epithelial cells (AECs) and alveolar macrophage cells (AMCs). SIGIRR knockdown may increase NF-κB activity via TRAF6 regulation by the classical but not the nonclassical NF-κB signaling pathway. Such modulation between TRAF6 and SIGIRR could affect cytokine secretion and exacerbate the immune response; the IL-8, NFKB1, and NFKBIA mRNA levels were reduced after SIGIRR overexpression. The current study reveals the molecular mechanisms of the negative regulatory roles of SIGIRR on the innate immune response related to the LPS/TLR-4 signaling pathway and provides evidence for strategies to clinically treat inflammatory diseases.
Highlights
Acute lung injury (ALI) is an acute hypoxic respiratory dysfunction resulting from multiple factors [1,2,3]
The results showed that obvious inhibition of the IL-8, NFKB1, and NFKBIA mRNA levels in alveolar macrophage cells (AMCs) was obtained after SIGIRR_cDNA transfection (Figure 3(e))
It has been demonstrated that suppression of LPS/Toll-like receptor-4 (TLR-4) greatly promotes the development of ALI
Summary
Acute lung injury (ALI) is an acute hypoxic respiratory dysfunction resulting from multiple factors [1,2,3]. The continuous progressive phase of ALI develops into acute respiratory distress syndrome (ARDS) [4, 5]. ALI has a poor prognosis and can rapidly progress to multiple organ failures with a 30%~70% mortality rate [6,7,8]. It has been proven that the lipopolysaccharide- (LPS-) Toll-like receptor-4 (TLR-4) signaling pathway plays a key role in the pathologic process of ALI [9,10,11]. Suppression of the LPS/TLR-4-mediated innate immune response is highly effective for the control of ALI
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