Journal article
Involvement of nitric oxide in IFN-γ-mediated reduction of microvessel smooth muscle cell proliferation
Molecular immunology, Vol.32(13), pp.965-973
09/01/1995
DOI: 10.1016/0161-5890(95)00062-J
PMID: 7477002
Abstract
Previous studies in our laboratory demonstrated that murine cerebral microvessel smooth muscle cells (SMC) activate syngeneic CD4
+ T-cells
in vitro. These T-cells, or their culture supernatants, in turn, strongly inhibit proliferation of the SMC. The present study focuses on IFN-γ as a mediator of inhibition of SMC proliferation, and addresses the molecular mechanism of this inhibition. IFN-γ profoundly reduced the proliferation of murine brain microvessel smooth muscle cells
in vitro. Three lines of evidence indicate that nitric oxide contributed to this effect: (1) IFN-γ-mediated inhibition of proliferation correlated with the quantity of nitrite, a stable breakdown product of nitric oxide, in culture supernatants; (2) the addition of N
g-monomethyl-
l-arginine, an inhibitor of nitric oxide synthesis, restored proliferation to control or near control levels; and (3) the addition of hemoglobin, which has a high affinity for, and thus sequesters nitric oxide, also resulted in significant restoration of the proliferative response. However, the nitric oxide donating chemical sodium nitroprusside, at concentrations up to 100 μM, had no direct cytostatic effect. These results suggest that nitric oxide is a necessary but insufficient component in IFN-γ-mediated inhibition of microvessel smooth muscle cell proliferation. TNF-α also stimulated nitric oxide production by the smooth muscle cells, but was not as potent as IFN-γ at inhibiting proliferation. Knowledge of the physiological effects of lymphokines on cells of the brain microvasculature will contribute towards a better understanding of inflammatory processes in diseases such as multiple sclerosis and infectious encephalitis.
Details
- Title: Subtitle
- Involvement of nitric oxide in IFN-γ-mediated reduction of microvessel smooth muscle cell proliferation
- Creators
- Colleen S. Stein - University of IowaZsuzsa Fabry - University of IowaSean Murphy - University of IowaMichael N. Hart - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular immunology, Vol.32(13), pp.965-973
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/0161-5890(95)00062-J
- PMID
- 7477002
- ISSN
- 0161-5890
- eISSN
- 1872-9142
- Language
- English
- Date published
- 09/01/1995
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984618518402771
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