Here we identify that PPAR-γ expression in AM is crucial to suppress pulmonary inflammation and diseases and to promote fast host recovery from IAV and RSV infections.
We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation.
Moreover, we found that PPARγ activation not only inhibited CS/LPS-induced TLR2/4 expression and <i>miR-27-3p</i>-mediated TLR2/4 signaling cascades involving the nuclear factor-κB (NF-κB), c-Jun NH<sub>2</sub>-terminal kinase (JNK)/p38, and Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathways in AMs but also ameliorated CS/LPS-induced AM activation and pulmonary inflammation.
Curcumin Attenuates Pulmonary Inflammation in Lipopolysaccharide Induced Acute Lung Injury in Neonatal Rat Model by Activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) Pathway.
These results suggested that H<sub>2</sub>S exposure can lead to Th1/Th2 immune imbalance, repress the anti-inflammatory effect of PPAR-γ/HO-1, and then activate NF-κB pathway-related genes and the downstream genes to aggravate pneumonia induced by LPS.
Rosiglitazone induces HO-1 expression via either NOX/ROS/c-Src/Pyk2/Akt-dependent Nrf2 activation or PPARγ in HPAEpiCs and suppresses LPS-mediated inflammatory responses, suggesting that PPARγ agonists may be useful for protection against pulmonary inflammation.
Conditional knockout of PPARγ in APCs using Cd11c-Cre Pparg(flox/flox) mice led to spontaneous lung inflammation and emphysema that resembled the phenotype of smoke-exposed mice.