Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts.
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.


METHODS
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-gamma, western blotting was performed. Cell proliferation was determined by counting cells following trypan blue staining. Media levels of IL-1beta, TNF-alpha, and IL-6 were quantified using ELISA.


RESULTS
IFN-gamma receptor 2 and IFN-alpha receptor 1, but not IFN-gamma 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-gamma had a greater effect to inhibit cell proliferation by D1 and D2 cells. In addition, IFN-gamma treatment increased the phosphorylation of STAT1 and MAPK in D1 cells as compared to normal fibroblasts. Also, the presence of exogenous IFN-gamma in the growth medium significantly induced IL-6, but not IL-1beta or TNF-alpha, in D1 and D2 cells.


CONCLUSIONS
Taken together, our results are consistent with hypersensitive reactions to IFN-gamma seen in patients with Down syndrome and may provide useful information to elucidate the mechanisms of IFN-gamma activities in those individuals.
Iwamoto
Tsutomu
T
Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Aoba-ku, Sendai 980-8575, Japan. tiwamoto@m.tains.tohoku.ac.jp
Yamada
Aya
A
Yuasa
Kenji
K
Fukumoto
Emiko
E
Nakamura
Takashi
T
Fujiwara
Taku
T
Fukumoto
Satoshi
S
D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004314:Down Syndrome / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D053583:Interleukin-1beta; D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human