Abstract
BackgroundRecent evidence has shown that C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in acute lung injury (ALI). Macrophages are key factors in the pathogenesis of ALI. The aim of this study was to investigate the role of CXCR4 in macrophages after lipopolysaccharide (LPS) stimulation and confirm that CXCR4 knockdown can inhibit inflammatory cytokines by suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathway activation.ResultsIn this study, we found that CXCR4 expression in lung tissue of ALI was significantly increased using immunofluorescence. We also found that the expression of CXCR4 in macrophages sorted from bronchoalveolar lavage fluid (BALF) of ALI was obviously upregulated through RT-qPCR. After CXCR4 knockdown using siRNA, we found that the expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was obviously down regulated in macrophages. Additionally, the phosphorylation of p38, Erk, and p65 was significantly decreased after CXCR4 knockdown through western blotting.ConclusionsTaken together, the present study suggests that CXCR4 knockdown may inhibit inflammatory cytokine expression in macrophages by suppressing MAPK and NF-κB signaling pathway activation. Therefore, CXCR4 knockdown may have potential clinical value in treating ALI.
Highlights
Recent evidence has shown that C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in acute lung injury (ALI)
We found that large numbers of macrophages infiltrated the lung tissue of ALI mice using immunofluorescence (Fig. 1a)
We found that the expression of CXCR4 in ALI lung tissue was increased through immunofluorescence compared with that of the normal group (Fig. 1b)
Summary
Recent evidence has shown that C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in acute lung injury (ALI). The aim of this study was to investigate the role of CXCR4 in macrophages after lipopolysaccharide (LPS) stimulation and confirm that CXCR4 knockdown can inhibit inflammatory cytokines by suppressing mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathway activation. Intrapulmonary inflammatory response caused by a large number of inflammatory cells into the lung is an important feature. The activation of alveolar macrophages and the release of inflammatory cytokines are the important causes of inflammation and development [9]. Macrophages were polarized to M1 macrophages induced by LPS stimulation and secreted a large number of inflammatory mediators and cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and macrophage. TNF-α can directly damage pulmonary vascular endothelium cells, lead to capillary endothelial permeability, and cause pulmonary edema. IL-6 can predict the severity of ALI [10]
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