Interferon-gamma-induced JAK2 and STAT1 signalling in a human salivary gland cell line.
We have used a human salivary gland cell line (HSG) as a possible in vitro model to evaluate the effects of IFN-gamma on human salivary gland epithelium (Wu et al., 1994, 1996, 1997). In the present study, we examined the JAK-STAT signal-transduction pathway in IFN-gamma-treated HSG cells. We demonstrate that JAK2 and Stat1 are phosphorylated at tyrosine residues in a time- and concentration-dependent manner following exposure to IFN-gamma. In addition, we show that activation of this signalling pathway is decreased by the addition of a blocking antibody to the IFN-gamma receptor. The same maneuver is also able to reduce by approximately 50-70% the surface expression of two IFN-gamma-induced immunoregulatory molecules: HLA-DR and ICAM-1. These results demonstrate that the JAK2 and Stat1 signalling pathway is active in salivary-derived epithelial cells and may contribute to their immunopathologic destruction.
Wu
A J
AJ
Clinical Investigations and Patient Care Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland, USA. ajwu2@aol.com
Chen
Z J
ZJ
Kan
E C
EC
Baum
B J
BJ
D000906:Antibodies / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D053614:Janus Kinase 2; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors / Q000276:immunology; D050794:STAT1 Transcription Factor; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D000096743:Interferon gamma Receptor
D000906:Antibodies; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D053614:Janus Kinase 2; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human; C507924:JAK2 protein, human