Premium
Differential Regulation of IL‐27 Expression during Inflammatory Stress in Adipocytes
Author(s) -
Nam Heesun,
Ferguson Bradley S,
Rainey Claire F,
Hopkins Robin G,
Stephens Jacqueline M,
Morrison Ron F
Publication year - 2010
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.24.1_supplement.476.6
Subject(s) - proinflammatory cytokine , adipocyte , tumor necrosis factor alpha , inflammation , adipose tissue , microbiology and biotechnology , adipokine , biology , endocrinology , medicine , chemistry , insulin resistance , immunology , insulin
Obesity can lead to insulin resistance by mechanisms involving macrophage infiltration of adipose tissue and adipocyte secretion of inflammatory adipokines that mediate systemic inflammation and disease. Interleukin‐27 is a heterodimeric cytokine encoded by independent p28 and EBI3 genes. While recent reports have demonstrated regulation of IL‐27 in antigen presenting cells, little information regarding IL‐27 in other cell types has emerged. Using 3T3‐L1 adipocytes stimulated with proinflammatory stimuli as a model of inflammatory stress, we demonstrate similar basal expression of p28 and EBI3 in undifferentiated preadipocytes (PAs) relative to mature adipocytes (ADs). Exposure of PAs to 100 pM tumor necrosis factor α (TNFα) resulted in marked, transient induction of p28 and EBI3 gene expression peaking at 4 hrs and 18 hrs, respectively. Interestingly, neither gene was induced equivalently in ADs following TNFα stimulation. Using specific inhibitors of pertinent signaling pathways, we determined that p28 and EBI3 were predominantly downstream of NFκB. However, the refractory nature of both genes in ADs was not likely due to differences in upstream signaling pathways that were similarly activated in PAs and ADs. These findings demonstrate that IL‐27 gene expression is regulated in PAs in response to inflammatory stress and that both p28 and EBI3 become refractory to such stress as PAs mature into ADs.