NDLI: Enhanced Anti-Inflammatory Effects of Cu, Zn-Superoxide Dismutase Delivered by Genetically Modified Skin Fibroblasts In Vitro and In Vivo

Content Provider	Springer Nature Link
Author	Okumura, Katsuhiko Nishiguchi, Kohshi Tanigawara, Yusuke Mori, Sachiko Iwakawa, Seigo Komada, Fusao
Copyright Year	1997
Abstract	Purpose. The purpose of this work was to evaluate the anti-inflammatory effects of secretable human Cu, Zn-superoxide dismutase (hSOD) delivered by genetically modified skin fibroblasts in vitro and in vivo. Methods. Rat skin fibroblasts were transfected with pRc/CMV-ILSOD including secretable SOD-coding cDNA. The effects of host and transformants on oxidative stress in vitromodels using the xanthine/xanthine oxidase (X/XO) system were examined to study the paracrine SOD action. The anti-inflammatory effects by transplantation of host and transformants were evaluated in an acute inflammation model, carrageenin-induced paw edema, in rats. Results. The transformants (ILSOD cells) secreted SOD protein into the extracellular space, and the extracellular SOD activity in ILSOD cells cultures was significantly increased compared with that in host cell cultures. ILSOD cells diminished the cytotoxic activity by X/XO in a paracrine fashion. These protective effects of ILSOD cells against X/XO-induced cytotoxicity correlated well with the decrease in lipid peroxidation in the damaged cells. The in vivo study showed that transplantation of ILSOD cell suspensions into the hind paw in rats inhibited carrageenin-induced paw edema for at least 7 days, and the degree and the durability of these inhibitory effects were dependent on the number of ILSOD cells transplanted. These inhibitory effects of ILSOD cell suspensions were reduced by co-administration of antiserum for hSOD. Furthermore, the healing of paw edema caused by carrageenin was markedly enhanced by transplantation of ILSOD cells into the edemics hind paw. Conclusions. The findings suggested that genetically modified skin fibroblasts are a suitable delivery system for obtaining an efficient and continuous supply of SOD to the target site, and this strategy may be a useful drug delivery system for therapeutic proteins.
Starting Page	1223
Ending Page	1227
Page Count	5
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	14
Issue Number	9
e-ISSN	1573904X
Language	English
Publisher	Kluwer Academic Publishers-Plenum Publishers
Publisher Date	1997-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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