Pathways of IL-8 release by adipose tissue

Abstract

The release of inflammatory factors from adipose tissue has been suggested to be the culprit in obesity-related cardiac and diabetic disease. We have demonstrated IL-8 release in vitro by human visceral adipose tissue explants previously. Our purpose is to explore the possible pathways related to IL-8 release over short-term incubations from visceral adipose tissue. Freshly isolated visceral adipose tissue is removed during laparoscopic gastric bypass from patients with a BMI > 40 ( n = 6). The tissue was immediately minced with scissors and incubated for 4 h in a shaking water bath. ELISA was utilized for IL-8 measurements. Four known pathways of IL-8 release were explored with their respective inhibitors: NF-κB pathway (NF-κB activation inhibitor), JNK pathway (JNK inhibitor II), p38 kinase pathway (SB 220025), and ERK kinase pathway with (UO126). Paired t-test was utilized for comparisons. The table displays that concurrent inhibition of the NF-κB pathway, the JNK pathway, the p38 pathway, and the ERK pathway resulted in almost complete inhibition of IL-8 release by explants of human adipose tissue over a 4-h incubation. IL-8 release was not completely inhibited by any one inhibitor. These data indicate that up regulation of IL-8 release observed in vitro of human visceral adipose tissue is due to at least three different known pathways that regulate IL-8 release. More importantly, IL-8 release is not activated by just one pathway. Further studies are needed to examine what activates these pathways in adipose tissue.