Generation of a Transgenic Mouse with Lung-specific Overexpression of the Human Interleukin-1 Receptor Antagonist Protein

Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 04/1998; 18(3):429-34. DOI: 10.1165/ajrcmb.18.3.2983
Source: PubMed


The purpose of the studies described here was to test the hypothesis that overexpression of the human interleukin-1 receptor antagonist (IL-1ra) in the distal airway epithelia of mice would result in amelioration of the inflammatory effects of IL-1alpha. The coding region of the human IL-1ra gene was placed under transcriptional control of the 5' flanking region of the human SP-C gene. Transgenic mice were generated by pronuclear injection of the transgene and identified by Southern blot analysis of genomic DNA. RNA expression of the transgene was confirmed by Northern blot analysis. In order to determine whether expression of the transgene conferred protection against inflammatory stimuli, control and transgenic mice were treated with IL-1alpha by intratracheal instillation. Six hours after treatment, bronchoalveolar lavage was performed, which revealed a statistically significant decrease in the degree of neutrophilia in the transgenic mice as compared with control mice. Furthermore, there was a significant reduction in the whole-lung myeloperoxidase concentration. Reverse transcription-polymerase chain reaction analysis of whole-lung RNA revealed a significant reduction in the messenger RNA/beta-actin ratio of macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-2 in the transgenic animals as compared with controls. The results of these studies indicate that distal airway epithelial cell expression of human IL-1ra results in partial protection from IL-1alpha-induced airway inflammation and injury.

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    • "IL-1β or TNF-α expression can lead to increased IL-16 expression by epithelial cells (Little et al., 2003) a cytokine with an immunomodulatory role in asthmatic inflammation (De Bie et al., 2002; McFadden et al., 2007). IL-1Ra is an antagonist to IL-1α/β signaling in the lung (Wilmott et al., 1998). It is produced at high levels by neutrophils in response to LPS stimulation or exposure to TNF-α (McColl et al., 1992; Nguyen et al., 2010) and in a guinea pig model of late asthmatic reactions (Okada et al., 1995). "
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    ABSTRACT: Plant based products represent a promising alternative to conventional treatments for inflammation. Moringa oleifera Lam is a tree rich in proteins, vitamins, minerals and a variety of phytochemcals with health benefits. Among the reported health benefits are antioxidant and anti-inflammatory properties. The purpose of this study was to investigate whether tea brewed from dried Moringa leaves would abrogate inflammation in a mouse model of acute lung inflammation induced by LPS or extracts prepared from dust collected from a swine confinement facility (DE). Mice were offered water or Moringa tea for seven days. Tea consumption was significantly greater than that of water consumption on days 1 and 6, but there were no significant differences in weight gain or food consumption. On day seven, mice from both groups were forced to inhale, via intranasal challenge, either Phosphate Buffered Saline (PBS), Lipopolysaccharide (LPS) [10 µg mL-1] or DE [10%]. Compared to mice that drank water, mice that drank Moringa tea had significantly less protein (p<0.05) and cellular influx (p<0.0001) into the lung after inhalation of 10% DE. No difference in neutrophil migration into the lungs of water and M. tea groups after LPS or DE challenge was detected. But mice that drank tea had significantly (p<0.05) more neutrophils with apoptotic morphology after DE challenge. TNF-α expression 24 h after inhalation of 10% DE, was significantly higher (p<0.05) in lungs of M. tea mouse group as compared to water group. This increase in TNF-α was accompanied by higher levels of pro and anti-inflammatory cytokines. Finally, activation of c-Jun N-terminal Kinase (JNK) in lungs of M. tea+DE group 24 h post inhalation was decreased. Taken together these results suggest that Moringa oleifera leaf tea exerts anti-inflammatory properties on acute lung inflammation induced by swine confinement dust through a mechanism involving neutrophil regulation and JNK activation.
    American journal of immunology 01/2014; 10(2):73. DOI:10.3844/ajisp.2014.73.87
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    • "Following an endotoxin challenge serum levels of IL-1 are decreased in IL-1Ra-null mice and increased in IL-1Ra overproducers in comparison to controls (Hirsch et al., 1996). Transgenic mice with distal airway epithelial cell expression of human IL-1Ra were partially protected from IL-1-induced airway inflammation and injury (Wilmott et al., 1998). "
    Chapter: IL-1Ra
    Academic Press.
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    Expert Opinion on Investigational Drugs 08/2003; 12(7):1067-86. DOI:10.1517/13543784.12.7.1067 · 5.53 Impact Factor
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