M. Laniadoschwartzman et al., HEME OXYGENASE INDUCTION WITH ATTENUATION OF EXPERIMENTALLY-INDUCED CORNEAL INFLAMMATION, Biochemical pharmacology, 53(8), 1997, pp. 1069-1075
Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regul
ates cellular levels of heme and hemeproteins; certain of the latter,
i.e. cytochrome P450s, generate pro-inflammatory products from endogen
ous substrates. Two HO isozymes, the products of distinct genes, have
been described; HO-1 is the inducible one, whereas HO-2 is believed to
be constitutively expressed. We studied the inducing effects of sever
al metal compounds [CoCl2, SnCl2, ZnCl2, heme, and cobalt protoporphyr
in (CoPP)] on HO-1 mRNA content and enzyme activity in cultures of rab
bit corneal epithelial (RCE) cells; these metal compounds are known to
induce HO in other tissues. Additionally, we studied HO-1 expression
in an experimental model of ocular inflammation produced in rabbit cor
neas by extended contact lens wear, and the relation of HO expression
to the induced inflammatory process. SnCl2 added to RCE cells in vitro
produced marked time- and concentration-dependent increases in HO-1 m
RNA and HO-1 enzyme activity; CoCl2, ZnCl2, and CoPP were inducers of
HO as well, though to a lesser degree than SnCl2. Corneas treated for
6 days with contact lenses impregnated with SnCl2 displayed substantia
lly less corneal inflammation, swelling, and new vessel invasion than
did controls; attenuation of ocular inflammation was paralleled by SnC
l2-induced increases in HO mRNA and HO activity in corneal epithelial
cells from treated eyes. It is suggested that amelioration of the infl
ammatory response produced by extended contact lens wear is due, in pa
rt, to the induction of high levels of HO-1 activity by SnCl2, which r
esults in diminished production of pro-inflammatory mediators generate
d through heme dependent metabolic processes. Regulation of HO activit
y in this manner may have clinical applications. (C) 1997 Elsevier Sci
ence Inc.