Inhibition of IFN-gamma-inducible protein-10 abrogates colitis in IL-10-/- mice.
A deficiency in understanding the steps responsible for colitis is the lack of comprehension for the role chemokines play in mucosal inflammation. IFN-gamma-inducible protein-10 (IP-10) and CXCR3 are highly expressed at sites of colitis. Our findings show that IP-10 significantly contributes to the development of Th1 and inflammatory responses. Specifically, IP-10 inhibition in IL-10(-/-) mice attenuates the associated increases in serum and/or local amyloid A, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-1alpha, and IL-1beta with colitis as compared with IL-10(-/-) mice that develop colitis similar to human Crohn's disease. Correspondingly, the rate or intensity of inflammation in IL-10(-/-) mice treated with anti-IP-10 Abs showed improved scoring of inflammation, compared with control IL-10(-/-) mice. This study provides important and novel information regarding IP-10 as a target for the treatment of colitis.
Singh
Udai P
UP
Department of Microbiology and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Singh
Shailesh
S
Taub
Dennis D
DD
Lillard
James W
JW
D000818:Animals; D001053:Apolipoproteins / Q000096:biosynthesis / Q000097:blood; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000172:deficiency* / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004760:Enterocolitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005243:Feces / Q000737:chemistry; D005260:Female; D007106:Immune Sera / Q000008:administration & dosage; D007116:Immunization, Passive / Q000379:methods; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis / Q000097:blood / Q000145:classification; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011817:Rabbits; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D000685:Serum Amyloid A Protein / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D015431:Weight Loss / Q000235:genetics / Q000276:immunology
D001053:Apolipoproteins; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D016207:Cytokines; D007106:Immune Sera; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D000685:Serum Amyloid A Protein; D007371:Interferon-gamma