Regulation of chemokine production via oxidative pathway in HeLa cells.
Inflammation is associated with disease progression and, by largely unknown mechanisms, has been said to drive oncogenesis. At inflamed sites, neutrophils deploy a potent antimicrobial arsenal that includes proteinases, antimicrobial peptides, and ROS. Reactive oxygen species (ROSs) induce chemokines. In the present study, the concentrations of IL-8 in culture supernatants of HeLa cells treated with ROS were determined by enzyme-linked immunosorbent assay. We used o-phenanthroline to deplete Fe(2+) in order to investigate the mechanisms through which ROSs induce IL-8 secretion in our system. The iron chelator o-phenanthroline effectively inhibited H(2)O(2)-induced ERK2 activation. Enzyme-linked immunosorbent assays showed that IL-8 protein secretion was elevated in ROS-treated HeLa cells. When Fe(2+) was removed from these cells, IL-8 secretion was inhibited. Collectively, these results indicate that Fe(2+)-mediated Erk pathway activation is an important signal transduction pathway in ROS-induced IL-8 secretion in epithelial cells.
Kina
Shinichiro
S
Department of Clinical Neuroscience Oral and Maxillofacial Functional Rehabilitation, University of Ryukyus, Nishihara, Okinawa 903-0215, Japan.
Nakasone
Toshiyuki
T
Takemoto
Hiroyuki
H
Matayoshi
Akira
A
Makishi
Shoko
S
Sunagawa
Nao
N
Liang
Feixin
F
Phonaphonh
Thongsavanh
T
Sunakawa
Hajime
H
D000890:Anti-Infective Agents / Q000494:pharmacology; D018925:Chemokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D016209:Interleukin-8 / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D000890:Anti-Infective Agents; D018925:Chemokines; D016209:Interleukin-8; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D007501:Iron; D048049:Extracellular Signal-Regulated MAP Kinases; D010100:Oxygen; C025205:1,10-phenanthroline