Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apolipoproteins / biosynthesis
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Apolipoproteins / blood
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Chemokine CXCL10
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Chemokines, CXC / antagonists & inhibitors*
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Chemokines, CXC / biosynthesis
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Chemokines, CXC / deficiency*
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Chemokines, CXC / immunology
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Cytokines / biosynthesis
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Enterocolitis / genetics*
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Enterocolitis / immunology
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Enterocolitis / pathology
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Enterocolitis / prevention & control*
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Feces / chemistry
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Female
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Immune Sera / administration & dosage
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Immunization, Passive / methods
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Immunoglobulin A / analysis
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Immunoglobulin A / blood
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Immunoglobulin G / analysis
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / blood
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Immunoglobulin G / classification
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Injections, Intraperitoneal
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Interferon-gamma / antagonists & inhibitors*
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Interferon-gamma / pharmacology*
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Interleukin-6 / biosynthesis
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Interleukin-6 / blood
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Rabbits
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Receptors, CXCR3
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Receptors, Chemokine / biosynthesis
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Serum Amyloid A Protein / biosynthesis
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Up-Regulation / genetics
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Up-Regulation / immunology
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Weight Loss / genetics
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Weight Loss / immunology
Substances
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Apolipoproteins
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CXCR3 protein, human
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Chemokine CXCL10
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Chemokines, CXC
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Cxcr3 protein, mouse
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Cytokines
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Immune Sera
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Immunoglobulin A
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Immunoglobulin G
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Interleukin-6
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Receptors, CXCR3
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Receptors, Chemokine
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Serum Amyloid A Protein
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Interferon-gamma