Synergistic induction of CXCL10 by interferon-gamma and lymphotoxin-alpha in astrocytes: Possible role in cerebral malaria

被引：10
作者：
Bakmiwewa, Supun M. [1 ,2 ]
Weiser, Silvia [1 ,2 ]
Grey, Meredith [1 ,2 ]
Heng, Benjamin [3 ]
Guillemin, Gilles J. [3 ]
Ball, Helen J. [1 ,2 ]
Hunt, Nicholas H. [1 ,2 ]
机构：
[1] Univ Sydney, Mol Immunopathol Unit, Sch Med Sci, Discipline Pathol, Sydney, NSW 2006, Australia
[2] Univ Sydney, Sydney Med Sch, Bosch Inst, Sydney, NSW 2006, Australia
[3] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia
来源：
CYTOKINE | 2016年 / 78卷
基金：
英国医学研究理事会; 澳大利亚研究理事会;
关键词：
Cerebral malaria; Astrocytes; Interferon-gamma; Lymphotoxin-alpha; CXCL10; TUMOR-NECROSIS-FACTOR; PERIPHERAL LYMPHOID ORGANS; COGNITIVE IMPAIRMENT; NONCEREBRAL MALARIA; MONOCLONAL-ANTIBODY; KYNURENINE PATHWAY; ENDOTHELIAL-CELLS; IMMUNE-RESPONSES; MICE DEFICIENT; BLOOD-STAGE;
D O I：
10.1016/j.cyto.2015.11.024
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Cerebral malaria (CM) has a high mortality rate and incidence of neurological sequelae in survivors. Hypoxia and cytokine expression in the brain are two mechanisms thought to contribute to the pathogenesis of CM. The cytokines interferon (IFN)-gamma and lymphotoxin (LT)-alpha and the chemokine CXCL10 are essential for the development of CM in a mouse model. Furthermore, serum IFN-gamma protein levels are higher in human CM than in controls, and CXCL10 is elevated in both serum and cerebrospinal fluid in Ghanaian paediatric CM cases. Astrocytes actively participate in CNS pathologies, becoming activated in response to various stimuli including cytokines. Astrocyte activation also occurs in murine and human CM. We here determined the responsiveness of mouse and human astrocytes to MN-7 and LT-alpha, with the aim of further elucidating the role of astrocytes in CM pathogenesis. Initially we confirmed that Ifn-gamma and Cxcl10 are expressed in the brain in murine CM, and that the increased Cxcl10 expression is IFN-gamma-dependant. IFN-gamma induced CXCL10 production in human and murine astrocytes in vitro. The degree of induction was increased synergistically in the presence of LT-alpha IFN-gamma induced the expression of receptors for LT-alpha, while LT-alpha increased the expression of the receptor for IFN-gamma, in the astrocytes. This cross-induction may explain the synergistic effect of the two cytokines on CXCL10 production. Expression of these receptors also was upregulated in the brain in murine CM. The results suggest that astrocytes contribute to CM pathogenesis by producing CXCL10 in response to IFN-gamma and LT-alpha. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：79 / 86
页数：8
相关论文
共 55 条
[1]   ASTROCYTIC CELL CLONES DERIVED FROM ESTABLISHED CULTURES OF 8-DAY POSTNATAL MOUSE CEREBELLA [J].
ALLIOT, F ;
PESSAC, B .
BRAIN RESEARCH, 1984, 306 (1-2) :283-291
[2]   Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children [J].
Armah, Henry B. ;
Wilson, Nana O. ;
Sarfo, Bismark Y. ;
Powell, Michael D. ;
Bond, Vincent C. ;
Anderson, Winston ;
Adjei, Andrew A. ;
Gyasi, Richard K. ;
Tettey, Yao ;
Wiredu, Edwin K. ;
Tongren, Jon Eric ;
Udhayakumar, Venkatachalam ;
Stiles, Jonathan K. .
MALARIA JOURNAL, 2007, 6 (1)
[3]   Control of pathogenic CD8+ T cell migration to the brain by IFN-γ during experimental cerebral malaria [J].
Belnoue, E. ;
Potter, S. M. ;
Rosa, D. S. ;
Mauduit, M. ;
Gruener, A. C. ;
Kayibanda, M. ;
Mitchell, A. J. ;
Hunt, N. H. ;
Renia, L. .
PARASITE IMMUNOLOGY, 2008, 30 (10) :544-553
[4]   CEREBRAL MALARIA - THE SEQUESTRATION HYPOTHESIS [J].
BERENDT, AR ;
TURNER, GDH ;
NEWBOLD, CI .
PARASITOLOGY TODAY, 1994, 10 (10) :412-414
[5]   Induction of IP-10 (CXCL10) in astrocytes following Japanese encephalitis [J].
Bhowmick, Sourojit ;
Duseja, Rachna ;
Das, Sulagna ;
Appaiahgiri, Mohan Babu ;
Vrati, Sudhanshu ;
Basu, Anirban .
NEUROSCIENCE LETTERS, 2007, 414 (01) :45-50
[6]   Cognitive impairment after cerebral malaria in children: A prospective study [J].
Boivin, Michael J. ;
Bangirana, Paul ;
Byarugaba, Justus ;
Opoka, Robert O. ;
Idro, Richard ;
Jurek, Anne M. ;
John, Chandy C. .
PEDIATRICS, 2007, 119 (02) :E360-E366
[7]   Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria [J].
Campanella, Gabriele S. V. ;
Tager, Andrew M. ;
El Khoury, Joseph K. ;
Thomas, Seddon Y. ;
Abrazinski, Tabitha A. ;
Manice, Lindsay A. ;
Colvin, Richard A. ;
Lustert, Andrew D. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (12) :4814-4819
[8]   THE CYTOKINE THEORY OF HUMAN CEREBRAL MALARIA [J].
CLARK, IA ;
ROCKETT, KA .
PARASITOLOGY TODAY, 1994, 10 (10) :410-412
[9]   The crossroads of neuroinflammation in infectious diseases: endothelial cells and astrocytes [J].
Combes, Valery ;
Guillemin, Gilles J. ;
Chan-Ling, Tailoi ;
Hunt, Nicholas H. ;
Grau, Georges E. R. .
TRENDS IN PARASITOLOGY, 2012, 28 (08) :311-319
[10]   Expression of chemokines and their receptors in human and simian astrocytes:: Evidence for a central role of TNFα and IFNγ in CXCR4 and CCR5 modulation [J].
Croitoru-Lamoury, J ;
Guillemin, GJ ;
Boussin, FD ;
Mognetti, B ;
Gigout, LI ;
Chéret, A ;
Vaslin, B ;
Le Grand, R ;
Brew, BJ ;
Dormont, D .
GLIA, 2003, 41 (04) :354-370
123456