Heme oxygenase induction with attenuation of experimentally induced corneal inflammation.
Heme oxygenase (HO), by catabolizing heme to bile pigments, down-regulates cellular levels of heme and hemeproteins; certain of the latter, i.e. cytochrome P450s, generate pro-inflammatory products from endogenous 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 several metal compounds [CoCl2, SnCl2, ZnCl2, heme, and cobalt protoporphyrin (CoPP)] on HO-1 mRNA content and enzyme activity in cultures of rabbit 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 corneas 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 mRNA 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 substantially less corneal inflammation, swelling, and new vessel invasion than did controls; attenuation of ocular inflammation was paralleled by SnCl2-induced increases in HO mRNA and HO activity in corneal epithelial cells from treated eyes. It is suggested that amelioration of the inflammatory response produced by extended contact lens wear is due, in part, to the induction of high levels of HO-1 activity by SnCl2, which results in diminished production of pro-inflammatory mediators generated through heme-dependent metabolic processes. Regulation of HO activity in this manner may have clinical applications.
Laniado-Schwartzman
M
M
The Rockefeller University Hospital, New York, NY 10021, U.S.A.
Abraham
N G
NG
Conners
M
M
Dunn
M W
MW
Levere
R D
RD
Kappas
A
A
D000818:Animals; D002460:Cell Line / Q000201:enzymology; D003261:Contact Lenses; D003315:Cornea / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D007634:Keratitis / Q000201:enzymology* / Q000209:etiology / Q000517:prevention & control; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D017971:Tin Compounds / Q000008:administration & dosage / Q000494:pharmacology*
D012333:RNA, Messenger; D017971:Tin Compounds; C023599:stannous chloride; D006419:Heme Oxygenase (Decyclizing)