TY - JOUR
T1 - Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts
AU - Iwamoto, Tsutomu
AU - Yamada, Aya
AU - Yuasa, Kenji
AU - Fukumoto, Emiko
AU - Nakamura, Takashi
AU - Fujiwara, Taku
AU - Fukumoto, Satoshi
N1 - Funding Information:
In conclusion, within the limits of the present findings, it may be concluded that Down syndrome derived fibroblasts highly express the IFN receptors IFNAR1 and IFNGR2. In addition, inhibition of cell proliferation, phosphorylation of STAT1, and production of IL-6 were strongly enhanced by IFN-γ in Down syndrome derived cells. These results emphasize the important roles of IFN-γ in Down syndrome patients and may be useful for understanding the molecular actions of IFN-γ in Down syndrome. Funding: This work was supported in part by grants-in-aid for Research Fellows of the Japan Society for the Promotion of Science from the Competing interests: None declared. Ethical approval: Not required. Ministry of Education, Science and Culture of Japan ( 17689058 and 20679006 to S. Fukumoto).
PY - 2009/10
Y1 - 2009/10
N2 - Objective: Down syndrome, a frequently encountered genetic disorder, is usually associated with medical problems related to infectious disease, such as periodontal diseases and prolonged wound healing. Although affected individuals are considered to have clinical problems related to high interferon (IFN) sensitivity, the molecular mechanisms of IFN activities are not completely understood. Design: Down syndrome derived fibroblasts, Detroit 539 (D1) and Hs 52.Sk (D2) cells, were used. To analyse the expressions of interferon (IFN) receptors and downstream of IFN-γ, western blotting was performed. Cell proliferation was determined by counting cells following trypan blue staining. Media levels of IL-1β, TNF-α, and IL-6 were quantified using ELISA. Results: IFN-γ receptor 2 and IFN-α receptor 1, but not IFN-γ receptor 1, were highly expressed in D1 and D2 cells, as compared to the control fibroblast cells. Cell proliferation by D1 and D2 cells was lower than that by the control fibroblasts, further, IFN-γ had a greater effect to inhibit cell proliferation by D1 and D2 cells. In addition, IFN-γ treatment increased the phosphorylation of STAT1 and MAPK in D1 cells as compared to normal fibroblasts. Also, the presence of exogenous IFN-γ in the growth medium significantly induced IL-6, but not IL-1β or TNF-α, in D1 and D2 cells. Conclusion: Taken together, our results are consistent with hypersensitive reactions to IFN-γ seen in patients with Down syndrome and may provide useful information to elucidate the mechanisms of IFN-γ activities in those individuals.
AB - Objective: Down syndrome, a frequently encountered genetic disorder, is usually associated with medical problems related to infectious disease, such as periodontal diseases and prolonged wound healing. Although affected individuals are considered to have clinical problems related to high interferon (IFN) sensitivity, the molecular mechanisms of IFN activities are not completely understood. Design: Down syndrome derived fibroblasts, Detroit 539 (D1) and Hs 52.Sk (D2) cells, were used. To analyse the expressions of interferon (IFN) receptors and downstream of IFN-γ, western blotting was performed. Cell proliferation was determined by counting cells following trypan blue staining. Media levels of IL-1β, TNF-α, and IL-6 were quantified using ELISA. Results: IFN-γ receptor 2 and IFN-α receptor 1, but not IFN-γ receptor 1, were highly expressed in D1 and D2 cells, as compared to the control fibroblast cells. Cell proliferation by D1 and D2 cells was lower than that by the control fibroblasts, further, IFN-γ had a greater effect to inhibit cell proliferation by D1 and D2 cells. In addition, IFN-γ treatment increased the phosphorylation of STAT1 and MAPK in D1 cells as compared to normal fibroblasts. Also, the presence of exogenous IFN-γ in the growth medium significantly induced IL-6, but not IL-1β or TNF-α, in D1 and D2 cells. Conclusion: Taken together, our results are consistent with hypersensitive reactions to IFN-γ seen in patients with Down syndrome and may provide useful information to elucidate the mechanisms of IFN-γ activities in those individuals.
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U2 - 10.1016/j.archoralbio.2009.07.009
DO - 10.1016/j.archoralbio.2009.07.009
M3 - Article
C2 - 19700144
AN - SCOPUS:69449085855
VL - 54
SP - 963
EP - 969
JO - Archives of Oral Biology
JF - Archives of Oral Biology
SN - 0003-9969
IS - 10
ER -
