Th2 cytokine-induced upregulation of 11β-hydroxysteroid dehydrogenase-1 facilitates glucocorticoid suppression of proasthmatic airway smooth muscle function

Abstract

Hu A, Fatma S, Cao J, Grunstein JS, Nino G, Grumbach Y, Grunstein MM. Th2 cytokine-induced upregulation of 11␤-hydroxysteroid dehydrogenase-1 facilitates glucocorticoid suppression of proasthmatic airway smooth muscle function.

Upregulation of 11β-hydroxysteroid dehydrogenase 1 in lymphoid organs during inflammation in the rat

“…Relatively little is known about 11HSD1, particularly in immune cells [29], but it is conceivable that cytokines modulate 11HSD1 transcription. In airway smooth muscle, IL-13 caused the upregulation of 11HSD1 via the activation of AP-1 coupled to MAPK signaling via the ERK1/2 and JNK pathways [40].…”

11β-Hydroxysteroid dehydrogenase type 1 is an important regulator at the interface of obesity and inflammation

“…According to these studies, CCAAT-enhancer-binding proteins (C/EBPs) appear to assume a basal role in the regulation of HSD11B1 expression, as they contribute to TNF-␣-, IL-1␤-, cAMP-, and glucocorticoidinduction, the latter being additionally mediated by the GR [80,81,83,84,[131][132][133][134]. Further studies suggest a significant role of the transcription factor activator protein-1 (encoded by JUN, see Table 1) in mediating upregulation by IL-13 and TNF-␣ [79,84,135]. A role for the nuclear receptors PPAR␣ and PPAR␥ was suggested, as corresponding agonists affect HSD11B1 expression [14,[117][118][119][120][121][122][123][124].…”

Elevated hepatic 11β-hydroxysteroid dehydrogenase type 1 induces insulin resistance in uremia

“…The Hepatic glucocorticoid levels and 11βHSD1 reductase activity were measured as previously described (48). Full methodology is discussed in SI Methods.…”