title: Proinflammatory adipocytokines induce TIMP-1 expression in 3T3-L1 adipocytes.
abstract: Tissue inhibitor of metalloproteinase (TIMP)-1 is an adipocyte-secreted protein upregulated in obesity which promotes adipose tissue development. Furthermore, the proinflammatory adipocytokines tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6 induce insulin resistance, and plasma concentrations are increased during weight gain. In the current study, the impact of TNFalpha and IL-6 on TIMP-1 mRNA and protein expression was determined in 3T3-L1 adipocytes. Interestingly, TNFalpha and IL-6 induced TIMP-1 protein secretion more than 3- and 2-fold, respectively. Furthermore, TIMP-1 mRNA was upregulated in a time- and dose-dependent fashion. Inhibitor experiments suggested that nuclear factor kappaB and p 44/42 mitogen-activated protein kinase are involved in both, basal and adipocytokine-induced TIMP-1 expression. Moreover, the thiazolidinedione troglitazone partly reversed TNFalpha- but not IL-6-induced TIMP-1 synthesis. Taken together, we demonstrate that TIMP-1 expression is selectively upregulated in fat cells by proinflammatory adipocytokines and might play a role in maintaining adipose tissue mass in obesity.
authors.affiliation: University of Leipzig, Department of Internal Medicine III, Ph.-Rosenthal-Str. 27, 04103 Leipzig, Germany.
authors.forename: Susan
authors.initials: S
authors.lastname: Kralisch
authors.forename: Johannes
authors.initials: J
authors.lastname: Klein
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lossner
authors.forename: Matthias
authors.initials: M
authors.lastname: Bluher
authors.forename: Ralf
authors.initials: R
authors.lastname: Paschke
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Mathias
authors.initials: M
authors.lastname: Fasshauer
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D002839:Chromans; D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077288:Troglitazone