Induction of iNOS mRNA by interferon-gamma in epithelial cells is associated with growth arrest and differentiation
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1Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston 77555-1019, USA.
Abstract:
Induction of inducible nitric oxide synthase (iNOS) mRNA by interferon-gamma (IFNgamma) is well established in various cell types. We observed earlier that this induction is differentiation-dependent in human keratinocytes. Since IFNgamma-mediated growth arrest and differentiation are separable but interrelated processes in keratinocytes, iNOS might play a role in their regulation. We conducted a series of in vitro experiments on normal and transformed epithelial cells with different tissue origins. We found that immortalization and transformation can influence the IFNgamma-mediated iNOS inducibility, but this process is tissue-specific as the induction correlates with the ability of the cells to differentiate.
Insights
Interferon-gamma (IFNγ) induces nitric oxide synthase (iNOS) in a differentiation-dependent manner in human keratinocytes. This induction is influenced by cell immortalization and transformation, and is tissue-specific, correlating with differentiation capacity.
Area of Science:
- Cell biology
- Immunology
- Molecular biology
Background:
- Interferon-gamma (IFNγ) is known to induce inducible nitric oxide synthase (iNOS) mRNA in many cell types.
- iNOS induction by IFNγ in human keratinocytes is differentiation-dependent.
- IFNγ-mediated growth arrest and differentiation are linked processes in keratinocytes, suggesting a potential role for iNOS in their regulation.
Purpose of the Study:
- To investigate the role of iNOS in the regulation of IFNγ-mediated growth arrest and differentiation in epithelial cells.
- To determine how immortalization and transformation affect IFNγ-mediated iNOS inducibility.
- To explore the tissue-specific nature of iNOS induction by IFNγ.
Main Methods:
- In vitro experiments were conducted on normal and transformed epithelial cells from various tissue origins.
- Analysis of inducible nitric oxide synthase (iNOS) mRNA and protein levels following interferon-gamma (IFNγ) stimulation.
- Assessment of cell differentiation markers and growth arrest in response to IFNγ treatment.
Main Results:
- Immortalization and transformation can alter IFNγ-mediated iNOS inducibility in epithelial cells.
- The effect of immortalization and transformation on iNOS inducibility is tissue-specific.
- iNOS induction by IFNγ correlates with the cell's capacity for differentiation, regardless of normal or transformed status.
Conclusions:
- iNOS induction by IFNγ is a differentiation-dependent process in epithelial cells.
- Cellular immortalization and transformation modify iNOS inducibility in a tissue-specific manner.
- The ability of cells to differentiate is a key factor in regulating IFNγ-mediated iNOS expression.