Regulation of inducible nitric oxide synthase mRNA levels by differentiation and cytokines in human keratinocytes.
Inducible nitric oxide synthase (iNOS) transcription is regulated by cytokines and immune stimuli in various cell types. However, there are few data available on iNOS expression and regulation in keratinocytes, even though it can play a role in keratinocyte proliferation during inflammation following wound healing. Our studies demonstrated a differentiation-dependent regulation of iNOS transcription in human keratinocytes from epidermis but not in buccal mucosal cells, which are less differentiated. Different interferon (IFN) types (alpha and gamma) regulated skin keratinocyte iNOS mRNA levels in different ways, predominantly in a differentiation-dependent manner. TGFbeta1 and IFNalpha can antagonize IFNgamma related iNOS induction. However, the antagonistic effects of IFNalpha on IFNgamma differ from those of TGFbeta1. Our studies demonstrate: (a) the presence of iNOS mRNA in human keratinocytes; (b) inducibility of iNOS mRNA by different cytokines; and (c) antagonism between certain cytokines in induction of iNOS mRNA. Further studies are needed to determine biological and therapeutical relevance of our findings.
Arany
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Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston 77555-1019, USA.
Brysk
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MM
Brysk
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Tyring
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SK
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D011994:Recombinant Proteins; D012867:Skin; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase