PMID- 15188138 OWN - NLM STAT- MEDLINE DCOM- 20040716 LR - 20190722 IS - 0046-8177 (Print) IS - 0046-8177 (Linking) VI - 35 IP - 6 DP - 2004 Jun TI - Expression of interleukin-18 by nasopharyngeal carcinoma cells: a factor that possibly initiates the massive leukocyte infiltration. PG - 722-8 AB - Interleukin-18 (IL-18) is a single-chain cytokine that is produced by various cells. With interleukin-12 (IL-12), it synergistically stimulates activated T cells and natural killer (NK) cells to produce interferon-gamma (IFN-gamma). Nasopharyngeal carcinoma (NPC) is the most common form of nasal and nasopharyngeal malignancy, and in NPC tumor tissues there is an intense leukocyte infiltration comprising predominantly T cells and macrophages. We previously showed an increased expression of IFN-gamma in the infiltrating T cells. To identify the cells that provide IL-12 and IL-18 for stimulating the expression of IFN-gamma in activated T cells, NPC cell lines CNE-2 and HK-1, as well as biopsies obtained from NPC and control individuals, were examined. CNE-2 and HK-1 cells were found to express messenger RNA encoding IL-18, but not IL-12. Secreted IL-18 was detected in the culture supernatant. Addition of a caspase-1 inhibitor decreased the secretion level, indicating that this IL-18 secretion was caspase-1 dependent. Moreover, the in vitro IL-18 production in NPC cell lines correlated with the NPC tumor cells in situ. NPC tumor cells in the biopsies produced IL-18, as detected by immunohistochemistry and immunofluorescent double staining. In contrast, IL-18 expression was not observed in the control biopsies. We suggest that IL-18 secreted by NPC tumor cells plays a role in initiating the leukocyte infiltration process. IL-18 stimulates T cells and NK cells to produce IFN-gamma, which consequently activates macrophages and other immune cells to secrete chemokines to start a leukocyte recruitment cascade. FAU - Hu, Huaizhong AU - Hu H AD - Department of Microbiology, Faculty of Medicine, National University Medical Institute, National University of Singapore, Singapore, Singapore. FAU - Tang, Kin Fai AU - Tang KF FAU - Chua, Yen Ni AU - Chua YN FAU - Lu, Jinhua AU - Lu J FAU - Feng, Ping AU - Feng P FAU - Chew, Chuan Tieh AU - Chew CT FAU - Chan, Soh Ha AU - Chan SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Hum Pathol JT - Human pathology JID - 9421547 RN - 0 (Enzyme Inhibitors) RN - 0 (Interleukin-18) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - Caspase 1/metabolism MH - Cell Line, Tumor MH - Cell Movement MH - Enzyme Inhibitors/pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Immunohistochemistry MH - Interleukin-18/*biosynthesis MH - Leukocytes/*metabolism MH - Nasopharyngeal Neoplasms/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2004/06/10 05:00 MHDA- 2004/07/17 05:00 CRDT- 2004/06/10 05:00 PHST- 2004/06/10 05:00 [pubmed] PHST- 2004/07/17 05:00 [medline] PHST- 2004/06/10 05:00 [entrez] AID - S0046817704001091 [pii] AID - 10.1016/j.humpath.2004.01.026 [doi] PST - ppublish SO - Hum Pathol. 2004 Jun;35(6):722-8. doi: 10.1016/j.humpath.2004.01.026.