Proposed schematic representation of the signaling pathway involved in the TNF-α-induced NOX/MAPK/c-JUN/NF-κB/COX-2 signaling impaired by G6PD knockdown in A549 cells.

Physiologically, stimulus by a low dosage of TNF-α causes cellular ROS production through the activation of NOX and downstream signaling (MAPK/NF-κB). The activated NOX/MAPK/c-JUN/NF-κB signaling is concomitant with the increased expression of COX-2 and production of PGE₂. G6PD knockdown results in the reduced generation of cellular NADPH and an impairment of TNF-α-induced NOX activation. Consequently, COX-2 expression and PGE₂ production are also less in G6PD-knockdown cells, suggesting the participation of G6PD in the TNF-α-induced inflammatory response against viral infection.