Inflammatory effect of endosulfan via NF-kappaB activation in macrophages.
Macrophages are essential for the inflammatory response process because they release a wide variety of proinflammatory mediators. Endosulfan is extremely toxic to invertebrates and has been implicated in various mammalian toxicities. However, its influence on production of cytokine or on the functions of macrophages is unclear. This study examined the effects of endosulfan on the production of nitric oxide (NO) and proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha), and examined the molecular mechanism in macrophages. Exposing macrophages to endosulfan induced the production of NO and proinflammatory cytokines and the expression of these genes. The transient transfection and electrophoretic mobility shift assays with the NF-kappaB binding sites showed that the NF-kappaB transcription factor mediated the endosulfan-induced increase in the expression levels of iNOS and proinflammatory cytokines. These results show that endosulfan stimulates the production of NO and proinflammatory cytokines and can up-regulate the gene expression levels through NF-kappaB transactivation. Overall, these results suggest that endosulfan has inflammatory potential.
Han
Eun Hee
EH
BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea.
Hwang
Young Pil
YP
Kim
Hyung Gyun
HG
Jeong
Hye Gwang
HG
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004726:Endosulfan / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics
D016207:Cytokines; D007306:Insecticides; D016328:NF-kappa B; D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D004726:Endosulfan