Iron chelator differentially activates macrophage inflammatory protein-3alpha/CCL20 in immortalized and malignant human oral keratinocytes.
Macrophage inflammatory protein-3alpha (MIP-3alpha or CCL20) is an intriguing molecule in cancer immunotherapy, but MIP-3alpha expression and signalling are not well understood in oral cancer cells. We investigated CCL20 expression and signal transduction by treating immortalized human oral keratinocyte (IHOK) and oral cancer (HN4) cells with deferoxamine (DFO) and examined the mRNA expression of CCL20 using RT-PCR and ELISA. IHOK and HN4 cells treated with DFO showed increased mRNA and protein expression of CCL20, and the upregulation of DFO-induced CCL20 expression was higher in IHOK cells than in HN4 cells. Selective inhibitors of p38 and ERK1/2 abolished DFO-induced CCL20 expression in both IHOK and HN12 cells, and p38 and ERK1/2 inhibitors prevented DFO-induced degradation of I-kappaB and NF-kappaB activation. Activation of c-fos and c-jun also occurred following DFO treatment in IHOK and HN4 cells. Collectively, these results suggest that DFO-induced MIP-3alpha, which is involved in the MAP kinase, c-fos, c-jun, and NF-kappaB pathways, may be an important mediator of the antitumour immune response in oral keratinocytes and warrants consideration as a target molecule for oral cancer treatment.
Lee
Sun-Kyung
SK
Department of Oral and Maxillofacial Pathology, Wonkwang University, Iksan, South Korea.
Lee
Jun
J
Min
Seung-Ki
SK
Won
Dal-Ho
DH
Lee
You-Mee
YM
Lim
Hyun-Dae
HD
Lee
Wan
W
Pae
Hyun-Ock
HO
Chung
Hun-Taeg
HT
Jun
Chang-Duk
CD
Lee
Suk-Keun
SK
Kim
Eun-Cheol
EC
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D054418:Chemokine CCL20 / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
C108355:CCL20 protein, human; D054418:Chemokine CCL20; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D016328:NF-kappa B; C025314:ferric citrate; D003676:Deferoxamine