Document Detail


Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.
MedLine Citation:
PMID:  23460134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future.
Authors:
Jae-Sung Kim; Michael B Ellman; Dongyao Yan; Howard S An; Ranjan Kc; Xin Li; Di Chen; Guozhi Xiao; Gabriella Cs-Szabo; David W Hoskin; Doug D Buechter; Andre J Van Wijnen; Hee-Jeong Im
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  228     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-05-28     Completed Date:  2013-09-03     Revised Date:  2014-03-27    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1884-96     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cattle
Cell Survival / drug effects
Gene Expression Regulation / drug effects
Humans
Interleukin-1 / antagonists & inhibitors,  metabolism*
Intervertebral Disc / cytology,  metabolism*,  physiopathology
Lactoferrin / chemistry,  metabolism*,  pharmacology
Lipopolysaccharides / toxicity*
Low Back Pain / drug therapy*,  physiopathology
Mice
Organ Culture Techniques
Proteoglycans / biosynthesis,  drug effects
Rabbits
Grant Support
ID/Acronym/Agency:
R01 AR049069/AR/NIAMS NIH HHS; R01 AR054465/AR/NIAMS NIH HHS; R01 AR055915/AR/NIAMS NIH HHS; R01 AR062136/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-1; 0/Lipopolysaccharides; 0/Proteoglycans; 146897-68-9/lactoferricin B; EC 3.4.21.-/Lactoferrin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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