RGD Reference Report - Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF-κβ Pathway in Endotoxin-Induced Uveitis. - Rat Genome Database

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Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF-κβ Pathway in Endotoxin-Induced Uveitis.

Authors: Tang, Wenyi  Ma, Jun  Gu, Ruiping  Ding, Xinyi  Lei, Boya  Wang, Xin  Zhuang, Hong  Xu, Gezhi 
Citation: Tang W, etal., Cell Physiol Biochem. 2018;46(1):375-388. doi: 10.1159/000488472. Epub 2018 Mar 23.
RGD ID: 126781759
Pubmed: PMID:29590655   (View Abstract at PubMed)
DOI: DOI:10.1159/000488472   (Journal Full-text)


BACKGROUND/AIMS: Lipocalin 2 (LCN2), an important mediator of a variety of cellular processes, is involved in regulating the inflammatory response, but its roles in different inflammatory diseases are controversial. Because the role of LCN2 in ocular inflammation has been unclear until now, we explored the function of LCN2 in lipopolysaccharide (LPS)-induced ocular inflammation in vivo and in vitro.
METHODS: Endotoxin-induced uveitis (EIU) was induced in male Sprague Dawley rats by the intravitreal injection of LPS. The expression and location of LCN2 in the retina were detected with western blotting and immunohistochemistry, respectively. We determined the clinical scores for anterior inflammation, quantified the infiltrated inflammatory cells, and measured the pro-inflammatory factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured primary rat Müller cells were stimulated with LPS and the expression and secretion of LCN2 were measured with real-time PCR, western blotting, and an ELISA. After Müller cells were cotreated with LPS and LCN2 or PBS, the expression and secretion of TNF-α, IL-6, and MCP-1 were examined with realtime PCR, western blotting, and ELISAs. Western blotting and immunofluorescence were used to detect the phosphorylation and cellular distribution of nuclear factor kappaB (NF-κB) subunit p65.
RESULTS: In EIU, the expression of LCN2 was significantly upregulated in the retina, especially in the outer nuclear layer (mainly composed of Müller cells). LPS stimulation of cultured Müller cells also markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly reduced the clinical scores, inflammatory infiltration, and protein leakage in EIU, which correlated with the reduced levels of proinflammatory factors in the aqueous humor and retina. LCN2 treatment also reduced the expression and secretion of TNF-α, IL-6, and MCP-1 in LPS-stimulated Müller cells. LCN2 inhibited the inflammatory response by inhibiting the phosphorylation and translocation of NF-κB p65.
CONCLUSIONS: LCN2 protects against ocular inflammation, at least in part, by negatively regulating the activation of the NF-κB signaling pathway. LCN2 may be a promising anti-inflammatory therapy for ocular diseases, such as uveitis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LCN2Humanuveitis  ISOLcn2 (Rattus norvegicus)protein:increased expression:retina and M��ller cellRGD 
Lcn2Ratuveitis  IEP protein:increased expression:retina and M��ller cellRGD 
Lcn2Mouseuveitis  ISOLcn2 (Rattus norvegicus)protein:increased expression:retina and M��ller cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Lcn2  (lipocalin 2)

Genes (Mus musculus)
Lcn2  (lipocalin 2)

Genes (Homo sapiens)
LCN2  (lipocalin 2)


Additional Information