Glucocorticoids (GC) influence immune responses, and exogenous GC are widely used clinically for their potent anti-inflammatory effects. Endogenous GC action is modulated by pre-receptor GC metabolising enzyme 11β-hydroxysteroid dehydrogenase (11b-HSD). 11b-HSD1 predominantly reactivates GCs, amplifying their action. Recent work has shown that 11b-HSD1 modulates immune and inflammatory response. However how innate immune system affect GC metabolism within cells remains largely unknown. Retinoic-acid-inducible gene I (RIG-I) is a cytosolic receptor that sense RNA viruses, such as influenza, producing cytokines and type 1 interferons. The aim of this study was to evaluate how RIG-I activation affect GC metabolism in human lung epithelial cells.
Methods: 5′-Triphosphate modified RNA (3pRNA), the ligand for RIG-I, was transfected by lipofection in human lung epithelial A549 cells. Cells were cultured for 24 h in the presence or absence of 1 μM cortisol following 3pRNA treatment. Cells were harvested. RNA was reverse transcribed and quantified by real-time PCR.
Results: Treatment of 3pRNA increased 11b-HSD1 and steroidogenic enzyme CYP11A1 mRNA levels (P<0.01), which were significantly increased by cortisol treatment. Interestingly combination treatment of 3pRNA and cortisol synergistically increased 11b-HSD1 mRNA levels (P<0.01). Pulmonary surfactant protein B (SP-B) mRNA levels were significantly increased by 3pRNA treatment. Cortisol also increased SP-B and SP-D mRNA levels (P<0.01). 3pRNA and cortisol treatments additively increased SP-B mRNA levels (P<0.01), showing similar pattern to 11b-HSD1 induction.
Conclusion: Innate immune receptor RIG-I may contribute to the amplification of GC action and could be important in the generation of pulmonary surfactant within lung cells. Further investigation may address the role of 11b-HSD1 during infection.