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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2011) 35, 407–415 (Printed in Great Britain)
Gaseous nitric oxide exhibits minimal effect on skin fibroblast extracellular matrix gene expression and immune cell viability
Alireza Moeen Rezakhanlou*†, Chris Miller‡, Bevin McMullin§, Abdi Ghaffari*, Rosa Garcia║ and Aziz Ghahary*1
*Department of Surgery, BC Professional Burn and Wound Healing Research Lab, Rm 350, Jack Bell Research Centre 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada, †School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran, ‡Division of Respiratory, Department of Medicine, University of British Columbia, Vancouver, BC, Canada, §Respiratory Services, Vancouver Coastal Health at Vancouver General Hospital, Vancouver, BC, Canada, and ║Department of Surgery, Vancouver Coastal Health Research Institute University of British Columbia, Vancouver, BC, Canada


NO (nitric oxide) molecule is produced by various mammalian cell types and plays a significant role in inflammation, infection and wound healing processes. Recently, gNO (gaseous nitric oxide) therapy has been utilized for its potential clinical application as an antimicrobial agent, with special focus on skin infection. In a previous study, we demonstrated that 200 ppm gNO, 8 h/day for three consecutive days significantly reduced the number of bacteria in dermal wounds without compromising the viability and function of skin cells. To increase the feasibility and ease of its clinical use, we propose that different doses of gNO (5 to 10 K ppm) for 8 h and as short as 10 min be used, respectively. To achieve this, we set up in vitro experiments and asked whether (i) different doses of gNO have any toxic effect on immune cells and (ii) gNO has any modulating effect on key ECM (extracellular matrix) components in fibroblasts. To further investigate the effect of gNO, expression of more than 100 key ECM genes have been examined using gene array in human fibroblasts. As immune cells play an important role in wound healing, the effect of gNO on proliferation and viability of human and mouse lymphocytes was also examined. The findings showed that, the 5, 25, 75 and 200 ppm of gNO for 8 h slightly increased the expression of Col 5A3 (collagen type V alpha 3), and gNO at 5 ppm decreased the expression of MMP-1 (matrix metalloproteinase 1), while exposure of fibroblast to 10 K ppm of gNO for 10 min does not show any significant changes in ECM genes. Exposure to gNO resulted in inhibition of lymphocyte proliferation without affecting the cell viability. Taken together, our findings show that skin could be treated with gNO without compromising the role of ECM and immune cells in low concentrations with long time exposure or high concentrations for a shorter exposure time.


Key words: extracellular matrix (ECM), fibroblast, gaseous nitric oxide, matrix metalloproteinase 1 (MMP-1), lymphocyte

Abbreviations: ConA, Concanavalin A, gNO, gaseous nitric oxide, ECM, extracellular matrix, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, GC, guanylyl cyclase, iNOS, inducible nitric oxide synthase, ITGB1, integrin beta-1, NO, nitric oxide, PHA, phytohaemagglutinin, UBC, University of British Columbia

1To whom correspondence should be addressed (email aghahary@interchange.ubc.ca).


Received 2 June 2010/10 November 2010; accepted 14 December 2010

Published as Cell Biology International Immediate Publication 14 December 2010, doi:10.1042/CBI20100420


© The Author(s) Journal compilation © 2011 Portland Press Limited


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)