Suppression of experimental autoimmune myasthenia gravis by inhibiting the signaling between IFN-gamma inducible protein 10 (IP-10) and its receptor CXCR3.
We have previously demonstrated that the chemokine IFN-gamma inducible protein 10 (IP-10) and its receptor CXCR3, are overexpressed in myasthenia gravis (MG) and its animal model experimental autoimmune MG (EAMG). We now studied the potential of modulating rat EAMG by interference in CXCR3/IP-10 signaling. Two different approaches were used: 1) blocking IP-10 by IP-10-specific antibodies and 2) inhibiting the CXCR3 chemokine receptor by a CXCR3 antagonist. Treatment by either of these reagents led to suppression of EAMG suggesting that inhibition of CXCR3/IP-10 signaling can be considered as a potential treatment modality for MG.
Feferman
Tali
T
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Aricha
Revital
R
Mizrachi
Keren
K
Geron
Erez
E
Alon
Ronen
R
Souroujon
Miriam C
MC
Fuchs
Sara
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
D000906:Antibodies; D054357:Chemokine CXCL10; D018925:Chemokines; C091326:Cxcl10 protein, rat; C515189:Cxcr3 protein, rat; D016207:Cytokines; D007155:Immunologic Factors; D012333:RNA, Messenger; D054367:Receptors, CXCR3