title: High-throughput multi-analyte Luminex profiling implicates eotaxin-1 in ulcerative colitis.
abstract: Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Veterans Affairs Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Coburn
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Veterans Affairs Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Horst
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Brown
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Veterans Affairs Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Allaman
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Brooks P
authors.initials: BP
authors.lastname: Scull
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Kshipra
authors.initials: K
authors.lastname: Singh
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Maithili V
authors.initials: MV
authors.lastname: Chitnavis
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Mallary E
authors.initials: ME
authors.lastname: Hodges
authors.affiliation: Department of Pediatrics, Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rosen
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Veterans Affairs Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Williams
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: James C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Dawn B
authors.initials: DB
authors.lastname: Beaulieu
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.affiliation: Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America ; Veterans Affairs Tennessee Valley Healthcare System, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000818:Animals; D054413:Chemokine CCL11 / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D005756:Gastritis / Q000097:blood / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010081:Oxazolone / Q000633:toxicity; D011446:Prospective Studies
chemical_list: D054413:Chemokine CCL11; D010081:Oxazolone