Epidemiological associations between early-life air pollution exposure and increased risk of inflammatory bowel diseases have been shown. Our aim was to determine if exposure to airborne particulate matter (PM10) during the neonatal period would alter colitis in the interleukin (IL)-10−/− mouse model.
IL-10−/− pregnant dams and pups were fed chow ± PM10 (9 μg/g) and pups were studied at 10, 14, and 20 weeks. Twenty-week-old mice were given 2% dextran sodium sulfate. Metagenomic analysis of stool was performed. Bacterial translocation was assessed by serum lipopolysaccharide and culturing bacteria from mesenteric lymph nodes and spleen. Cytokine expression was measured in gut homogenates using the MesoScale discovery platform. PM10 was applied to CMT93 cells ± J744 macrophages, and resistance and cytokine secretion were assessed. THP-1 macrophages were incubated with Escherichia coli HB101 ± PM10 for assessment of uptake and killing.
PM10 exposure increased colonic proinflammatory cytokines and bacterial translocation into mesenteric lymph nodes, whereas IL-17A levels were reduced in PM10-fed 10-week-old mice. Bifidobacterium was decreased in mice fed PM10, whereas serum lipopolysaccharide was increased. PM10 interfered with phagocytosis and killing in THP-1 cells. In coculture, PM10 increased tumor necrosis factor α and fluorescein isothiocyanate–dextran flux. After dextran sodium sulfate treatment, PM10-fed mice responded with increased colonic tumor necrosis factor α and IL-1β and a larger percentage of PM10-fed mice had live bacteria in the mesenteric lymph nodes.
Our data suggest that early exposure to pollution particulates can result in an earlier onset of intestinal disease in genetically susceptible hosts and can alter responses to gut injury in later life.
Article first published online 21 May 2014.Supplemental Digital Content is Available in the Text.
Departments of *Medicine, and
†Pediatrics, University of Alberta, Edmonton, AB, Canada;
‡Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada;
§Environmental Health Directorate, Health Canada, Ottawa, ON, Canada;
‖Department of Lab Medicine and Pathology, University of Alberta, Edmonton, AB, Canada; and
Departments of ¶Medicine, and
**Production Animal Health, University of Calgary, Calgary, AB, Canada.
Reprints: Karen L. Madsen, PhD, University of Alberta, 7-142K Katz Building, Edmonton, AB T6G 2C2, Canada (e-mail: email@example.com).
Research supported by The Alberta Inflammatory Bowel Disease Consortium and Alberta Innovates - Health Solutions. S.Y. Salim received fellowship support from Canadian Institutes of Health Research, Canadian Association of Gastroenterology, Crohn's and Colitis Foundation of Canada, and Alberta Innovates Health Solutions.
The authors have no conflicts of interest to disclose.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).
Received February 12, 2014
Accepted April 3, 2014