Inhibition of C5a receptor alleviates experimental CNS lupus

Alexander Jacob; Bradley Hack; Tao Bai; James R. Brorson; Richard J. Quigg; Jessy J. Alexander

doi:10.1016/j.jneuroim.2010.02.011

Inhibition of C5a receptor alleviates experimental CNS lupus

Alexander Jacob
, Bradley Hack
, Tao Bai
, James R. Brorson
, Richard J. Quigg
, Jessy J. Alexander

Medicine

The University of Chicago

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/. lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF- α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK. , pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/. lpr brains. MRL/. lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.

Original language	English
Pages (from-to)	46-52
Number of pages	7
Journal	Journal of Neuroimmunology
Volume	221
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2010.02.011
State	Published - Apr 2010

Keywords

Anaphylatoxins
Brain
Complement system
Inflammation
Systemic lupus erythematosus

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10.1016/j.jneuroim.2010.02.011

Cite this

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title = "Inhibition of C5a receptor alleviates experimental CNS lupus",

abstract = "To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/. lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF- α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK. , pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/. lpr brains. MRL/. lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.",

keywords = "Anaphylatoxins, Brain, Complement system, Inflammation, Systemic lupus erythematosus",

author = "Alexander Jacob and Bradley Hack and Tao Bai and Brorson, \{James R.\} and Quigg, \{Richard J.\} and Alexander, \{Jessy J.\}",

year = "2010",

month = apr,

doi = "10.1016/j.jneuroim.2010.02.011",

language = "English",

volume = "221",

pages = "46--52",

journal = "Journal of Neuroimmunology",

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}

TY - JOUR

T1 - Inhibition of C5a receptor alleviates experimental CNS lupus

AU - Jacob, Alexander

AU - Hack, Bradley

AU - Bai, Tao

AU - Brorson, James R.

AU - Quigg, Richard J.

AU - Alexander, Jessy J.

PY - 2010/4

Y1 - 2010/4

N2 - To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/. lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF- α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK. , pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/. lpr brains. MRL/. lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.

AB - To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/. lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF- α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK. , pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/. lpr brains. MRL/. lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.

KW - Anaphylatoxins

KW - Brain

KW - Complement system

KW - Inflammation

KW - Systemic lupus erythematosus

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U2 - 10.1016/j.jneuroim.2010.02.011

DO - 10.1016/j.jneuroim.2010.02.011

M3 - Article

C2 - 20207017

AN - SCOPUS:77951224132

SN - 0165-5728

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SP - 46

EP - 52

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

IS - 1-2

ER -

Inhibition of C5a receptor alleviates experimental CNS lupus

Abstract

Keywords

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