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R. Clark Lantz,
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Professor and Associate Head of Cell Biology and Anatomy,
Deputy Director, Southwest Environmental Health Science Center,
Ph.D., University of West Virginia, 1975.
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lantz@email.arizona.edu
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Pulmonary toxicology of air pollutants, especially metals;
effects of air pollutants on neonatal lung growth and development.
Research Activities
Exposure to environmental toxicants alters lung structure and
function and leads to impairment of the pulmonary defense mechanisms
in the lung. Current investigations are examining the effects
of arsenic exposure, acute smoke inhalation and environmental
tobacco smoke. Using lung slice technology, we have shown that
acute exposure to low mM concentrations of arsenic can activate
transcription factors and induce heat shock protein expression
in lung slices. Acute exposure to arsenite leads to increased
nuclear AP-1 expression. This increase was also associated with
increased expression of heat shock protein 32 (hemeoxygenase -1),
whose expression is regulated by AP-1. Using confocal immunohistochemistry,
we have been able to demonstrate that the increased expression
occurs in alveolar macrophages, type II epithelial cells and capillary
endothelial cells. Similar doses of arsenic did not show significant
increases in NFkB activation, indicating that AP-1 may play a
central role in arsenic-induced alterations of gene expression
in response to acute lung exposure.
Exposure to environmental pollutants may severely affect lung
growth and development. Our lab has been examining the effects
of arsenic exposure on embryonic rat lung structure and function.
Pregnant females have been exposed to 500 ppb as arsenic in the
drinking water from conception until embryonic day 18. Lungs have
been removed and analyzed for arsenic-induced alterations in gene
expression using subtractive hybridization techniques. Ongoing
analysis is identifying clones that have been isolated from these
procedures. Alterations in gene expression will be correlated
with alterations in structure and lung function.
In addition, we are currently investigating the effects of environmental
pollutants on pulmonary inflammation We have found that environmental
tobacco smoke causes changes in lung structure that are consistent
with inhibition of neonatal lung growth in rats. It is our hypothesis
that ETS will down regulate the expression of the anti-inflammatory
cytokine, interleukin-10 (IL-10), leading to increased inflammation
and tissue destruction. We are currently investigating this by
using IL-10 knockout mice. In addition, we are testing a new transgenic
mouse we have designed that constitutively expresses IL-10 in
airway epithelium of IL-10 knockout mice. We have been able to
demonstrate that acute exposure to a complex smoke results in
significant down regulation of IL-10 in humans, thus supporting
our hypothesis. We have also recently demonstrated that nitration
of IL-10, which can occur during inflammation, results in increased
biological activity of the protein.
Finally, because of our interest in the role of inflammation
in lung injury, we are currently evaluating the anti-inflammatory
activity of compounds isolated from three plants, turmeric, ginger
and boswellia, that have been extensively used in Indian medicine.
We have been able to demonstrate that extracts from these plants
are able to inhibit inflammatory mediator production in a dose
dependent manner. We are currently investigating the potential
sites of action of the active compounds.
Publications (Query PubMed for this investigator)
Lantz, R. Clark, Ranulfo Lemus, Robert W. Lange and Meryl H.
Karol. Rapid reduction of intracellular glutathione in human bronchial
epithelial cells exposed to occupational levels of toluene diisocyanate.
Toxicol. Sci. 60:348-355, 2001.
Wijeweera, Jayanthika B., A. Jay Gandolfi, Alan Parrish and R.
Clark Lantz. Sodium arsenite enhances AP-1 and NFkB DNA binding
and induces stress protein expression in precision-cut rat lung
slices. Toxicol. Sci. 61:238-294, 2001.
Burgess, Jefferey L., Christopher J. Nanson, Richard Gerkin,
Mark L. Witten, Tracy A. Hysong and R. Clark Lantz. Rapid decline
in sputum IL-10 concentration following occupational smoke exposure.
Inhalation Toxicol. 14:133-140, 2002
Freels, Jon L., Dan K. Nelson, Jeffrey C. Hoyt, Michael Habib,
Hiroki Numanami, R. Clark Lantz and Richard A. Robbins. Enhanced
activity of IL-10 after nitration in reducing IL-1 production
by stimulated peripheral blood mononuclear cells. J. Immunol.
(in press).
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