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Leucine and calcitriol modulation of human airway inflammation in lung endothelial cells
Author(s) -
Brown Patricia,
Johnstone Megan,
Zemel Michael B
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.46.8
Subject(s) - calcitriol , endocrinology , medicine , inflammation , nitric oxide , adipocyte , cytokine , chemistry , adipose tissue , biology , vitamin d and neurology
Airway inflammation is substantially increased by obesity‐induced alterations of adipocyte‐derived cytokines. Previous studies from our lab demonstrated that leucine and calcitriol stimulate opposing effects on systemic inflammation and cytokine production in adipocytes and muscle cells. Accordingly, we hypothesized that dietary calcium (via suppression of calcitriol) and leucine will suppress adipose tissue derived TNFα and increase adiponectin release, resulting in suppression of hypertrophic growth and attenuation of chronic airway inflammation. Human and murine adipocytes were treated with calcitriol (10 nM) and leucine (0.5 mM) for 48 h and the conditioned medium (CM) were applied to human microvascular endothelial cells of the lung (HMVEC‐L). Calcitriol CM increased expression of the adhesion molecule ICAM‐1 (p<0.04), and leucine treatment reversed this effect (p<0.02). TNFα receptor 1 and NFκB expression exhibited comparable effects. Similarly, calcitriol suppressed nitric oxide release by HMVEC‐L, while leucine reversed this effect (p<0.02). In similar experiments in human airway smooth muscles cells (HASMCs), leucine reduced IL‐1B gene expression by 60% (p <0.002) and PDGF‐D by 70% (p<0.001). Thus, leucine suppresses inflammatory cytokines, increases vasodilation, and may reduce asthma‐associated hypertrophy in HMVEC‐L and HAMSCs, while calcitriol exerts the opposite effect.