Leucine and calcitriol modulation of human airway inflammation and hyper‐reactivity

Abstract

Obesity alters the balance of adipose tissue‐derived cytokines and increases airway inflammation and hyper‐reactivity. We previously found calcitriol and leucine to exert opposing effects on adipose tissue cytokine production, systemic inflammation, and monocyte adherence to vascular endothelial cells. We now propose that dietary calcium (via suppression of calcitriol) and leucine attenuate airway inflammation and reactivity by suppressing adipose tissue TNF‐α and enhancing adiponectin release. Human adipocytes were treated with calcitriol (10 nM) and leucine (0.5 mM) for 48 h and the conditioned medium (CM) were applied to human airway smooth muscle cells (HASMC). Calcitriol CM induced a 7‐fold increase in human leukocyte adhesion to HASMC (p<0.001) which was associated with increased TNF‐α receptor, VCAM and NFκB expression (~50%, p<0.02). In contrast, leucine CM decreased leukocyte adhesion (~50%, p<0.001) and NFκB (24%, p<0.02) and VCAM (21%, p<0.05) and increased adiponectin receptor 2 expression (29%, p<0.05). HASMC reactivity was measured as contractile responses to KCl and histamine under physiological flow and shear. Calcitriol CM augmented contractile responses to both agonists by 50 – 70% (p<0.001), while leucine inhibited the contractile response to KCl by 43% (p<0.001). These data suggest dietary calcium and leucine may suppress airway inflammation and reactivity.