EGF activates PI3K-Akt and NF-kappaB via distinct pathways in salivary epithelial cells in Sjögren's syndrome.
Epidermal growth factor (EGF) exerts tropic effects on salivary epithelial cells. We examined EGF-mediated signaling pathways in the salivary epithelial cells of patients with Sjögren's syndrome (SS). We compared the immunohistochemical expression of EGF receptor (EGF-R), phosphatidylinositol 3-kinase (PI3K), Akt and nuclear factor kappa B (NF-kappaB) in the labial salivary glands of SS patients (n = 6) with those of control subjects (n = 2). EGF-mediated signaling pathways were further studied in vitro (n = 3) using primary salivary epithelial cells; NF-kappaB p65 nuclear translocation and Akt phosphorylation were examined by immunofluorescence and western blotting, respectively. The phosphorylation of EGF-R and Akt, and the nuclear expression of NF-kappaB p65, were increased in situ in the salivary epithelial cells of SS patients compared with those of control subjects. Epidermal growth factor induced rapid EGF-R phosphorylation and NF-kappaB p65 nuclear translocation in primary salivary epithelial cells in vitro. However, EGF also induced late Akt phosphorylation (after 12 h). Chemical inhibition of PI3K-Akt by LY294002/wortmannin did not affect EGF-mediated NF-kappaB p65 nuclear translocation; and NF-kappaB inhibition by Bay 11-7082 did not suppress Akt phosphorylation. Our data suggest that EGF stimulates both the PI3K-Akt pathway and NF-kappaB via distinct mechanisms, promoting tropic effects in SS salivary epithelial cells.
Nakamura
Hideki
H
The First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki City, Nagasaki, Japan. nhideki@nagasaki-u.ac.jp
Kawakami
Atsushi
A
Ida
Hiroaki
H
Koji
Takehiko
T
Eguchi
Katsumi
K
D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012235:Rhodamines / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology
D005456:Fluorescent Dyes; D016328:NF-kappa B; D011994:Recombinant Proteins; D012235:Rhodamines; C009434:tetramethylrhodamine isothiocyanate; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D016650:Fluorescein-5-isothiocyanate