Interaction of interferon-gamma and epidermal growth factor in the regulation of nitric oxide production and cellular proliferation in a cultured murine mammary cell line, COMMA-D.
The regulation of nitric oxide synthase (NOS) activity and gene expression by cytokines and growth factors has been studied using the murine mammary epithelial cell line, COMMA-D. NOS activity was stimulated by exposure to interferon-gamma (IFN-gamma) and could be further stimulated by tumour necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF) although neither was affective alone. The maximal activity observed in the presence of IFN-gamma and EGF was not affected by the order in which cells were exposed. Messenger RNA levels for the inducible NOS isoform were increased by IFN-gamma and TNF-alpha in a manner consistent with the elevation of NOS activity. EGF also stimulated thymidine incorporation into DNA which was attenuated by coexposure with IFN-gamma in a manner that appeared to be largely NO-independent.
Low
B C
BC
Department of Biochemistry and Centre for Gene Research, University of Otago, Dunedin.
Prosser
C G
CG
Lacasse
P
P
Grigor
M R
MR
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects; D013936:Thymidine / Q000737:chemistry
D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D013936:Thymidine