4‐HNE inhibits IL‐6 and IL‐8 expression through the Gαi‐dependent NF‐κB pathway. Secretion of the pro‐inflammatory cytokines IL‐6 and IL‐8 in (A) ARPE‐19 and (B) CCD‐841 cells was measured by elisa. *
P < 0.05 versus vehicle‐treated controls. 4‐HNE‐induced expression of IL‐6, IL‐8, Bax, Bcl‐2 and GPR109A was measured in ARPE‐19 cells in the presence of (C) non‐targeting or GPR109A siRNA or (D) inhibitors of NF‐κB and AP‐1. *
P < 0.05 versus vehicle‐targeting or non‐targeting siRNA‐transfected controls. #
P < 0.05 versus cells treated with 1 or 10 μM 4‐HNE. (E) Nuclear translocation of the transcription factors NF‐κB, c‐Fos and c‐Jun, and (F) expression levels of IL‐6, IL‐8, GPR109A and NOX4 were measured in ARPE‐19 cells pretreated with 8‐CPT‐cAMP or inhibitors of intracellular Ca2+ (BAPTA‐AM), NOX4 (VAS2870), ERK1/2 (PD98059), p38 (SB203580) and JNK (SP600125) prior to 4‐HNE treatment. *
P < 0.05 versus vehicle‐treated controls. #
P < 0.05 versus 4‐HNE‐treated cells.