Constitutive expression of interleukin-18 in head and neck squamous carcinoma cells.
BACKGROUND
Interleukin (IL)-18 is a potent immunomodulatory cytokine promoting TH-1 and cytotoxic immune responses through interferon (IFN)-gamma induction. The aim of this study was to investigate the production of IL-18 by squamous cell carcinoma of the head and neck (HNSCC).


METHODS
The expression of IL-18 was analyzed by reverse transcriptase-polymerase chain reaction, Western blot, and ELISA in untreated and 5-fluorouracil (5-FU)-treated HNSCC cell lines. Immunohistochemical analysis was performed on tumor specimens from 16 patients with primary invasive HNSCC.


RESULTS
We have demonstrated that HNSCC cell lines express IL-18 at the mRNA, as well as the protein, level. However, the IL-18 protein was expressed intracellularly and predominantly released as an unprocessed inactive 24-kDa form. After exposure to 5-FU, the processed form of IL-18 was detected in the supernatants of both HNSCC cell lines.


CONCLUSIONS
These results indicate that HNSCC cells are a potential source of IL-18 cytokine. The finding that the exposure to 5-FU can elicit its processing suggests a novel target for immunomodulatory intervention in patients with HNSCC.
Martone
Tiziana
T
Division of Otorhinolaryngology, Department of Clinical Pgysiopathology, University of Torino, via Genova 3, 10126 Torino, Italy. tiziana.martone@unito.it
Bellone
Graziella
G
Pagano
Marco
M
Beatrice
Fabio
F
Palonta
Francesca
F
Emanuelli
Giorgio
G
Cortesina
Giorgio
G
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005472:Fluorouracil / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D020382:Interleukin-18; D012333:RNA, Messenger; D020170:Caspase 1; D005472:Fluorouracil