Interleukin-8 production in human adipose tissue. inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin.
Obesity and Type 2 diabetes are associated with an increased risk of developing cardiovascular disease. Reports have suggested that the chemokine, interleukin-8, may be involved in the development of diabetic macroangiopathy as well as in the pathogenesis of atherosclerosis. Two classes of drugs, the biguanides and the insulin-sensitizing thiazolidinediones seem to have additional beneficial effects on cardiovascular risk-factors besides their effects on glucose homeostasis. In this study, we investigated the effects of the thiazolidinedione, Ciglitazone, the peroxisome proliferator-activated receptor alpha-agonist 5,8,11,14-eicosatetraynoic acid (ETYA) and the biguanide, Metformin on interleukin-8 gene expression and production in human adipose tissue in vitro. Ciglitazone 10-100 M inhibited interleukin-8 release by 25-33% (p < 0.05) and mRNA expression by 33-60% (p < 0.05). Metformin 0.1-10 mM inhibited interleukin-8 release by 20-50% (p < 0.05) and mRNA expression by 20-90% (p < 0.05). However, ETYA did not effect the production of interleukin-8 in the adipose tissue. In conclusion, we demonstrate the ability of two anti-diabetic compounds to decrease the release of interleukin-8 from human adipose tissue in vitro. These findings open the possibility that the beneficial effects on cardiovascular risk-factors of these anti-diabetic compounds might involve a reduction in the interleukin-8 produced in human adipose tissue.
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital and Faculty of Health Sciences, Aarhus University, Denmark. jmb@mail-online.dk
J M
JM
Bruun
S B
SB
Pedersen
B
B
Richelsen
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D046508:Culture Techniques; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008687:Metformin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D016209:Interleukin-8; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D015117:5,8,11,14-Eicosatetraynoic Acid; D008687:Metformin; C039671:ciglitazone