Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model

Objective

To investigate the role of Toll-like receptor 2 (TLR2), TLR4, TLR9 and myeloid differentiation factor 88 (MyD88) on alveolar macrophages in ventilator-induced lung injury (VILI).

Methods

Male, adult pathogen-free Sprague-Dawley rats weighing 300-350 g were used in this study. Animals were tracheotomized and allowed to breathe spontaneously for 4 h or mechanically ventilated for 4 h with low or high tidal volume (7 or 40 mL/kg). TLR2, TLR4, and TLR9, MyD-88 and NF-κΒ of alveolar macrophages’ expression under the different ventilation conditions were detected. Pulmonary permeability, lung inflammatory, IL-6 and IL-1β were assessed as well.

Results

Rats subjected to high tidal volume showed significantly greater pulmonary permeability and lung inflammatory than the control rats. Alveolar macrophages from rats subjected to high tidal volume also showed significantly higher protein expression of TLR2 (0.59±0.049 vs. 0.35±0.036 and 0.36±0.031, both P<0.001), TLR4 (0.845±0.0395 vs. 0.401±0.026 and 0.403±0.020, both P<0.001), TLR9 (0.727±0.074 vs. 0.383±0.039 and 0.367±0.043, both P<0.001), MyD-88 (1.01±0.060 vs. 0.485±0.045 and 0.507±0.046, both P<0.001) and NF-κΒ (0.776±0.067 vs. 0.448±0.043 and 0.481±0.047, both P<0.001), as well as significantly higher concentrations of IL-6 (7.32±0.24 vs. 2.42±0.13 and 2.44±0.32, both P<0.001) and IL-1β (139.95±9.37 vs. 53.63±5.26 and 53.55±6.63, both P<0.001) than the control and low tidal volume group.

Conclusions

The overexpression of TLR2, TLR4, and TLR9 on alveolar macrophages and release of pro-inflammatory cytokines play a role in VILI.