Involvement of multiple signaling pathways in the post-bariatric induction of IL-6 and IL-8 mRNA and release in human visceral adipose tissue.
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 3h 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 3h 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 TNFalpha receptor (etanercept) plus a blocking antibody against IL-lbeta reduced by 55% the increase in IL-6 mRNA and by 42% that of IL-8 mRNA seen between 1 and 5h of incubation. The upregulation of IL-8 and IL-6 mRNA accumulation as well as their release over a 2 or 4h incubation was reduced by around 50% in the presence of an inhibitor of the p38 MAPK or an inhibitor of the NFkappaB 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 TNFalpha and IL-1beta. 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 NFkappaB pathways.
Fain
John N
JN
Department of Molecular Sciences, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. jfain@utmem.edu
Bahouth
Suleiman W
SW
Madan
Atul K
AK
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery*; D046508:Culture Techniques; D003609:Dactinomycin / Q000494:pharmacology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009767:Obesity, Morbid / Q000378:metabolism / Q000601:surgery; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D048051:p38 Mitogen-Activated Protein Kinases; D000068800:Etanercept