Effects of Zinc Finger Protein A20 on Lipopolysaccharide (LPS)-Induced Pulmonary Inflammation/Anti-Inflammatory Mediators in an Acute Lung Injury/Acute Respiratory Distress Syndrome Rat Model

Abstract

BackgroundThe aim of this study was to investigate the effects of zinc finger protein A20 on lipopolysaccharide (LPS)-induced pulmonary inflammation/anti-inflammatory mediators in an acute lung injury/acute respiratory distress syndrome (ALI/ARDS) rat model.Material/MethodsForty-eight ALI/ARDS rats were selected and assigned into normal saline (NS) (injected with NS), LPS (injected with LPS), LPS-C1 (injected with pEGFP-C1, NS and LPS), and A20 groups (injected with pEGFP-C1-A20, NS, and LPS). The wet/dry (W/D) ratio of rat lung tissues and total protein concentration and the number of neutrophils in bronchoalveolar lavage fluid (BALF) were detected. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were applied to detect the protein and mRNA expressions of A20, IL-10, and TNF-α, respectively. Western blotting was employed to detect the protein expressions of A20, nuclear factor-kappa B (NF-κB) p65 and NF-κB p-P65 in rat lung tissues.ResultsCompared with the NS group, the W/D ratio of rat lung tissues and total protein concentration and the number of neutrophils in BALF in the other 3 groups increased significantly. The protein and mRNA expressions of A20, IL-10, and TNF-α were significantly higher in the LPS group than in the NS group. The protein and mRNA expressions of A20 and IL-10 were significantly up-regulated and the expression of TNF-α, NF-κB p65, and NF-κB p-P65 was significantly down-regulated in rats injected with A20 compared to those in the LPS group.ConclusionsThe study provided evidence that zinc finger protein A20 can alleviate pulmonary inflammation by inhibiting TNF-α, NF-κB p65, and NF-κB p-P65 expressions and promoting IL-10 expression.

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“…A20, encoded by the Tumour Necrosis Factor-α (TNFα) induced protein 3 gene (TNFAIP3), has emerged as a central negative regulator of NF-κB (122,133). Compared to other organs, A20 mRNA expression in the lung is relatively high (47) and protein levels are detectable in whole lung homogenate of rodents (132,145). A20 is rapidly induced after host TLR -pathogen interaction, and through interaction of TNFα and IL-1 family cytokines with their receptors.…”

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“…Therefore, zinc supplements may be helpful in preventing ventilator-induced lung injury in patients who require mechanical ventilation, which should be studied in the future. In addition to these, A20, a zinc-dependent protein, appears to play a role in alleviating ARDS, possibly due to its role in inhibiting TNF-α and NF-κB p65 and enhancing IL10 production [ 163 ]. All of these above-mentioned promising results suggest that adequate zinc levels may play a protective role against ARDS.…”

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