Abstract
AbstractThe treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site. In rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis, the fusion protein remained in the inflamed tissues and joints for about 1 week after injection, and the amelioration of local inflammation, disease progression and inflammatory pain in the animals were concomitant with homoeostatic preservation of the tissues and with the absence of global immune suppression. IDO-Gal3 may serve as an immunomodulatory enzyme for the control of focal inflammation in other inflammatory conditions.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases
United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs
U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
NSF | Directorate for Mathematical & Physical Sciences | Division of Materials Research
U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
Computer Science Applications,Biomedical Engineering,Medicine (miscellaneous),Bioengineering,Biotechnology
Cited by
14 articles.
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