Administration of nonviral gene vector encoding rat β‐defensin‐2 ameliorates chronic <i>Pseudomonas aeruginosa</i> lung infection in rats

Hu, Qinyong; Zuo, Peng; Lei, Lei; Yang, Shuo; Xu, Guo; Lan, Fang; Lu, Xin-Jiang; Xiong, Weining; Xu, Yu; Xiong, Sheng

doi:10.1002/jgm.1435

Cited by 12 publications

(10 citation statements)

References 59 publications

(87 reference statements)

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“…The reason may be that the concentration of rBD2 was not enough to affect normal cells in vivo . High rBD2 level helped to reduce pathologic change and tissue damage, and rBD2 knockdown aggravated inflammatory response, coincident with the results reported by other literature [20,21]. The main reason maybe the anti-bacteria function reduced the damage caused by pathogen, and its regulation of inflammatory factors reduced inflammation.…”

Section: Discussionsupporting

confidence: 85%

β-Defensin 2 Ameliorates Lung Injury Caused by Pseudomonas Infection and Regulates Proinflammatory and Anti-Inflammatory Cytokines in Rat

Shen

Lü

Zhao

et al. 2014

IJMS

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An important member of the defensin family, β-defensin 2, is believed to play an important role in defense against foreign pathogens. In the present study, we constructed lentiviral vectors to express and knockdown β-defensin 2 in rat lungs. The results showed that the infection of β-defensin 2 overexpression lentivirus and β-defensin 2 shRNA effectively increased and suppressed the expression of β-defensin 2 in rat lung, respectively. The overexpression of β-defensin 2 mediated by the lentiviral vector protected lung from infection of Pseudomonas aeruginosa, but shRNA targeting β-defensin 2 aggregated the damage of lung. In addition, we also found that β-defensin 2 overexpression increased basal expression of anti-inflammatory cytokine such as IL-4, IL-10 and IL-13 and decreased levels of proinflammatory cytokines which include IL-1α, IL-1β, IL-5, IL-6, IL-8, IL-18, and TNF-α. Moreover, in the process of cytokine regulation, NF-κB pathway may be involved. Taken together, these data suggest that β-defensin 2 has protective effects against infection of Pseudomonas aeruginosa in rat and plays a role in inflammatory regulation by adjusting cytokine levels.

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Section: Discussionsupporting

confidence: 85%

β-Defensin 2 Ameliorates Lung Injury Caused by Pseudomonas Infection and Regulates Proinflammatory and Anti-Inflammatory Cytokines in Rat

Shen

Lü

Zhao

et al. 2014

IJMS

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“…These findings are consistent with studies conducted by Wu et al (12) and Hu et al (29). The primary reasons may lie in the antibacterial function of increased rBD-2 and its regulation of inflammatory factors during bacterial infection and inflammation.…”

Section: Discussionsupporting

confidence: 94%

ATP serves an anti-inflammatory role by enhancing β-defensin-2 response in acute pneumonia of rat

Shen

Zhou

et al. 2017

Biomedical Reports

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The aim of the current study was to evaluate the effect of ATP on the expression of rat β-defensin-2 (rBD-2) in a time-dependent manner, as well as its therapeutic value in an acute pneumonia rat model. A total of 30 rats as a treatment group and 30 as a control group were treated with the same dose of ATP and normal saline, respectively, lung tissues were isolated from rat and expression of rBD-2 mRNA was assessed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 12, 24 and 36 h following treatment. Rats were divided into five groups: The control group treated with normal saline, the Pseudomonas aeruginosa (PA) infected group, group treated with ATP, group treated with cephalosporins, and the group treated with both ATP and cephalosporins. At 24 h following treatment, rat serum and lung tissues were collected for assessment of histological changes, and alterations to expression of the rBD-2 protein by immunohistochemistry, expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 proteins by ELISA. RT-qPCR results indicated that the expression of rBD-2 mRNA was upregulated in response to ATP stimulation in lung tissues of rat, reaching its highest peak at 24 h. Immunohistochemistry demonstrated that ATP treatment enhanced the expression of rBD-2 protein in rat lungs. Ceftazidime and ATP protected lungs from infection of PA and reduced the pathological damage of the lung. Overexpression of rBD-2 by ATP led to decreased protein expression of TNF-α and IL-6 in lung tissues and serum. ATP upregulates the expression of rBD-2 and serves an anti-inflammatory role in the acute pneumonia of a rat model.

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“…Therefore, major efforts have been directed toward developing non-viral vectors for these purposes. For example, the β-defensin-2 delivered to rat lungs by polyethylenimine can effectively inhibit Pseudomonas aeruginosa infection in the lung 84 . However, certain non-viral lipid or polymer formulations can also induce varying levels of inflammatory cytokines and their efficiency of gene transfer remains low.…”

Section: Gene Therapy For Ali/ardsmentioning

confidence: 99%

Gene Therapy for ALI/ARDS

Lin¹,

Dean²

2011

Critical Care Clinics

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by acute respiratory failure and are associated with diverse disorders, such as pulmonary edema, pneumonia, sepsis, trauma, shock and lung contusion. Gene therapy is a potentially powerful approach to treat a variety of diseases related to ALI/ARDS. Numerous viral and non-viral methods for gene delivery to the lung have been developed, although pulmonary architecture and immune activation represent barriers to successful gene transfer. In this review, recent advances in the development of more efficient viral and non-viral gene transfer systems are discussed. In addition, the current status of gene therapy applied to ALI/ARDS-associated pulmonary diseases is reviewed. With the development of more efficient gene therapy vectors, gene therapy is a promising strategy for clinical application in the not too distant future.

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Administration of nonviral gene vector encoding rat β‐defensin‐2 ameliorates chronic Pseudomonas aeruginosa lung infection in rats

Cited by 12 publications

References 59 publications

β-Defensin 2 Ameliorates Lung Injury Caused by Pseudomonas Infection and Regulates Proinflammatory and Anti-Inflammatory Cytokines in Rat

β-Defensin 2 Ameliorates Lung Injury Caused by Pseudomonas Infection and Regulates Proinflammatory and Anti-Inflammatory Cytokines in Rat

ATP serves an anti-inflammatory role by enhancing β-defensin-2 response in acute pneumonia of rat

Gene Therapy for ALI/ARDS

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