Effects of quorum sensing system lasR/rhlR gene on the expression of foxp3, TGF-β1 and IL-10 of lung tissue in tracheal intubation model rat with Pseudomonas aeruginosa biofilm infection / 解放军医学杂志

ABSTRACT

Objective To investigate the effects of lasR/rhlR gene on Foxp3, TGF-β1 and IL-10 of lung tissue in rat tracheal intubation model with biofilm infection of Pseudomonas aeruginosa (Ps. aer) wild strain (PAO1) and quorum sensing (QS) deficient strain (ΔlasRΔrhlR). Methods Twenty-one SD rats were randomly assigned into 3 groups (7 each) ΔlasRΔrhlR-treated group, PAO1-treated group and sterile control group. Biofilms (BF) were cultured in vitro, and the BF coated tube (infected respectively with Ps. aer PAO1 strain, ΔlasRΔrhlR strain, or with asepsis) was inserted into the trachea to establish the rat model. The rats were sacrificed on the 7th day after intubation. Colony count of lung tissue homogenate (cfu) and lung HE staining were performed, and IL-10 content in bronchoalveolar lavage fluid (BALF), TGF-β1 in lung tissue, and the expression of Foxp3 mRNA in lung cells were determined. Results The bacterial counts were significantly higher in PAO1 and ΔlasRΔrhlR groups than that in sterile control group, and the counts were obviously higher in PAO1 group (10400.00 ± 6313.70/g lung tissue) than that in ΔlasRΔrhlR group (975.00 ± 559.97/g lung tissue, P<0.05). There was no significant pathological changes in lung tissue in sterile control group, while the bronchi and blood vessels in PAO1 group were infiltrated by a large number of inflammatory cells and complicated with alveolar septum thickening and local abscess and necrosis. The pathological changes were milder in ΔlasRΔrhlR group than in PAO1 group; the expression of Foxp3 mRNA was higher in the two Ps. aer infected groups than that in sterile control group (0.65 ± 0.32), and it was significantly higher in PAO1 group (4.62 ± 1.07) than in ΔlasRΔrhlR group (2.15 ± 1.43, P<0.05). The accumulated optical density value of TGF-β1 was significantly higher in the two Ps. aer infected groups than in sterile control group (3721.66 ± 1412.95), and significantly higher in PAO1 group (65 090.56 ± 33 956.54) than that in ΔlasRΔrhlR group (28 861.99 ± 10 826.96, P<0.05); the level of IL-10 was significantly higher in the two Ps. aer infected groups than in that of sterile control group (57.43 ± 22.13ng/ml), and significantly higher in PAO1 group (188.07 ± 57.01ng/ml) than in ΔlasRΔrhlR group (93.31 ± 17.26ng/ml, P<0.05). Conclusion Ps. aer QS system lasR/rhlR gene may promote inflammation, up-regulate the Foxp3 expression and increase the TGF-β1 and IL-10 levels in lung tissue, which may prompt the protraction and persistence of infection.