Involvement of multiple signaling pathways in the post-bariatric induction of IL-6 and IL-8 mRNA and release in human visceral adipose tissue

• Published in: Biochemical pharmacology 2005-05, Vol.69 (9), p.1315-1324
• Main Authors: Fain, John N., Bahouth, Suleiman W., Madan, Atul K.
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adipose Tissue - cytology; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Adipose Tissue - surgery; Biological and medical sciences; Culture Techniques; Dactinomycin - pharmacology; Etanercept; Female; Humans; IL-1β; IL-6; IL-8; Immunoglobulin G - metabolism; Immunoglobulin G - pharmacology; Interleukin-1 - antagonists & inhibitors; Interleukin-6 - biosynthesis; Interleukin-6 - secretion; Interleukin-8 - biosynthesis; Interleukin-8 - secretion; Medical sciences; NF-kappa B - antagonists & inhibitors; NFΚB; Obesity, Morbid - metabolism; Obesity, Morbid - surgery; p38 MAPK; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; Pharmacology. Drug treatments; Receptors, Tumor Necrosis Factor - metabolism; RNA, Messenger - biosynthesis; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Signal Transduction; Time Factors; TNFα; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Up-Regulation - drug effects
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2005.02.009

The present studies were designed to determine the site of and the mechanism for the rapid increase in IL-6 and IL-8 mRNA observed in human visceral adipose tissue after removal during laparoscopic bariatric surgery. Upregulation of IL-6 and IL-8 mRNA as well as their release were seen within 3 h whether one intact piece of tissue or minced pieces of adipose tissue were incubated in vitro. Most of the IL-6 and IL-8 mRNA content of visceral adipose tissue after 3 h of incubation was in the non-fat cells. Actinomcyin D markedly reduced the upregulation of IL-6 and IL-8 mRNA. Incubation of adipose tissue explants with a soluble TNFα receptor (etanercept) plus a blocking antibody against IL-lβ reduced by 55% the increase in IL-6 mRNA and by 42% that of IL-8 mRNA seen between 1 and 5 h of incubation. The upregulation of IL-8 and IL-6 mRNA accumulation as well as their release over a 2 or 4 h incubation was reduced by around 50% in the presence of an inhibitor of the p38 MAPK or an inhibitor of the NFκB pathway and by 85% in the presence of both inhibitors. The data suggest that the relative trauma and/or hypoxia that occurs when adipose tissue is removed results in the release of TNFα and IL-1β. These cytokines, and probably other factors as well, enhance IL-6 and IL-8 mRNA accumulation in human adipose tissue explants through mechanisms involving the p38 MAPK and NFκB pathways