Document Detail


Differential role of lipocalin 2 during immune complex-mediated acute and chronic inflammation in mice.
MedLine Citation:
PMID:  23280250     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Lipocalin 2 (LCN-2) is an innate immune protein that is expressed by a variety of cells and is highly up-regulated during several pathologic conditions, including immune complex (IC)-mediated inflammatory/autoimmune disorders. However, the function of LCN-2 during IC-mediated inflammation is largely unknown. Therefore, this study was undertaken to investigate the role of LCN-2 in IC-mediated diseases.
METHODS: The up-regulation of LCN-2 was determined by enzyme-linked immunosorbent assay in 3 different mouse models of IC-mediated autoimmune disease: systemic lupus erythematosus, collagen-induced arthritis, and serum-transfer arthritis. The in vivo role of LCN-2 during IC-mediated inflammation was investigated using LCN-2-knockout mice and their wild-type littermates.
RESULTS: LCN-2 levels were significantly elevated in all 3 of the autoimmune disease models. Further, in an acute skin inflammation model, LCN-2-knockout mice exhibited a 50% reduction in inflammation, with histopathologic analysis revealing notably reduced immune cell infiltration as compared to wild-type mice. Administration of recombinant LCN-2 to LCN-2-knockout mice restored inflammation to levels observed in wild-type mice. Neutralization of LCN-2 using a monoclonal antibody significantly reduced inflammation in wild-type mice. In contrast, LCN-2-knockout mice developed more severe serum-induced arthritis compared to wild-type mice. Histologic analysis revealed extensive tissue and bone destruction, with significantly reduced neutrophil infiltration but considerably more macrophage migration, in LCN-2-knockout mice compared to wild-type mice.
CONCLUSION: These results demonstrate that LCN-2 may regulate immune cell recruitment to the site of inflammation, a process essential for the controlled initiation, perpetuation, and resolution of inflammatory processes. Thus, LCN-2 may present a promising target in the treatment of IC-mediated inflammatory/autoimmune diseases.
Authors:
Rangaiah Shashidharamurthy; Deepa Machiah; Jesse D Aitken; Kalyani Putty; Gayathri Srinivasan; Benoit Chassaing; Charles A Parkos; Periasamy Selvaraj; Matam Vijay-Kumar
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-05-22     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1064-73     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Acute-Phase Proteins / genetics,  immunology*,  metabolism
Animals
Antigen-Antibody Complex / immunology*,  metabolism
Arthritis, Experimental / immunology*,  metabolism
Chronic Disease
Dermatitis / immunology*,  metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Inflammation / immunology*,  metabolism
Lipocalins / genetics,  immunology*,  metabolism
Lupus Erythematosus, Systemic / immunology*,  metabolism
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Oncogene Proteins / genetics,  immunology*,  metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
K01 DK083275/DK/NIDDK NIH HHS; K01-DK-072564/DK/NIDDK NIH HHS; K01-DK-079392/DK/NIDDK NIH HHS; K01-DK-083275/DK/NIDDK NIH HHS; R01 DK072564/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Antigen-Antibody Complex; 0/Lipocalins; 0/Oncogene Proteins; 126469-30-5/Lcn2 protein, mouse
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