CD28 Deficiency Ameliorates Blast Exposure-Induced Lung Inflammation, Oxidative Stress, Apoptosis, and T Cell Accumulation in the Lungs via the PI3K/Akt/FoxO1 Signaling Pathway

Figure 7

Schematic representation of CD28 KO reverses lung blast injury by the PI3K/Akt/FoxO1 signaling pathway. Blast exposure induces the phosphorylation of the PI3K protein, which activates the Akt protein in C57BL/6 mice. Once Akt is activated, it induces p-FoxO1, a downstream target protein of Akt, which is dephosphorylated to form FoxO1 that is transferred to the nucleus. Therefore, we hypothesize that FoxO1 upregulates the expressions of IL-1β, IL-6, TNF-α, NF-κB, CD44, active Caspase-8, CD163, MDA5, IREα, Bax, and Caspase-3 expression and downregulates the expressions of IL-10, SOD-1, and Bcl-2, which regulates inflammation, oxidative stress, and apoptosis, while CD28 KO might reduce PI3K/Akt phosphorylation and increase FoxO1 phosphorylation, which reverses blast exposure-induced lung injury. WT: C57BL/6 wild-type mice; CD28^-/-: CD28 knockout mice.