Mechanisms involved in modulation of cytokine production in oral cells after herpes simplex virus type 1 infection

• Main Authors: Yu-Ching Teng, 鄧宇晴
• Other Authors: Shan-Ling Hung
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/26516130096953950059

碩士 === 國立陽明大學 === 口腔生物研究所 === 91 === Herpes simplex virus type 1 (HSV-1) usually causes oral infection, and results in gingivostomatitis and herpes labialis. Cytokine is one of the immune response against HSV-1 infection. HSV-1 induces expression of various cytokines in many different cell types, but little is known regarding cytokines expressed by oral cells after HSV-1 infection. The purposes of this study were to investigate the secretion of interleukin-6 (IL-6), IL-8 and IL-1β in gingival keratinocytes (GK) and gingival fibroblasts (GF) after HSV-1 infection and to examine the possible mechanisms involved. The cytokine production was measured by an enzyme-linked immunosorbent assay (ELISA). The results showed that HSV-1 induced IL-6 secretion in GF, but not in GK. This phenomenon was completely inhibited by serum which contained anti-HSV-1 antibody. The ultraviolet (UV)- or heat-treatment abolished the plaque forming activity of HSV-1. The UV- or heat-inactivated viruses were still able to induce IL-6 secretion in GF. This suggests that complete life cycle was not required to induce IL-6 secretion in GF. Moreover, purified viral gD alone was able to induce IL-6 secretion in GF. Inhibitors, pyrollidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC), against NF-κB pathway reduced IL-6 secretion of mock-infected and infected GF. HSV-1 infection also enhanced nuclear protein binding to the κB site DNA as analyzed by electrophoretic mobility shift assay (EMSA). The combined results suggest that induction of IL-6 by HSV-1 in GF may be through NF-κB pathway. In addition, HSV-1 induced IL-8 secretion in GF, whereas HSV-1 reduced IL-8 secretion in GK. IL-1β was not detected in GF and GK after HSV-1 infection. Finally, interferon-γ (IFN-γ) synergistically enhanced IL-6 secretion in GF that infected with HSV-1. However, IFN-γ upregulated IL-6 secretion on HSV-infected GF, but IFN-γ was not affect IL-8 secretion on infected GK. In conclusion, secretion of cytokines, IL-6 and IL-8, was different in GF and GK after HSV-1 infection. HSV-1 induced IL-6 secretion in GF through mechanisms involving NF-κB signal transduction pathway. Viral gD may induce IL-6 secretion in GF.