Transcription networks responsible for early regulation of Salmonella-induced inflammation in the jejunum of pigs

Journal of Inflammation

Research

Stéphanie Vastenhouw¹  Mari Smits²  Jan van der Meulen²  Agnes de Wit²  Marcel Hulst²  Theo Niewold³ 

[1] Central Veterinary Institute of Wageningen University and Research Centre, P.O. Box 65, 8200, Lelystad, AB, The Netherlands;Livestock Research of Wageningen University and Research Centre, P.O. Box 65, 8200AB, Lelystad, The Netherlands;Nutrition and Health, Katholieke Universiteit Leuven, Kasteelpark Arenberg 30, 3001, Heverlee, B, Belgium;

关键词: Transcription regulation;    Salmonella;    Pig intestine;   

DOI  :  10.1186/1476-9255-10-18

 received in 2012-10-17, accepted in 2013-04-10,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe aim of this study was to identify transcription factors/regulators that play a crucial role in steering the (innate) immune response shortly (within a few hours) after the first contact of the intestinal mucosa with an inflammatory mediator, and to test whether the processes regulated by these factors/regulators can be modulated by chemical substances of natural origin.MethodsWe experimentally induced inflammation by perfusion of surgically applied jejunal loops with Salmonella enterica subspecies enterica serovar Typhimurium DT104 in three pigs. Segments of mock and Salmonella treated loops were dissected after 2, 4 and 8 hours of perfusion. IL8 and IL1-beta mRNA expression levels were measured in mucosal scrapings of all segments. Furthermore, intra-animal microarray comparisons (isogenic) between Salmonella and mock treated segments after 8 hours, and inter-animal comparisons between similar Salmonella-treated loops of each pig at 2 and 4 hours, were performed.ResultsIL-1beta and IL8 mRNA levels, and intra-animal microarray comparisons at 8 hours between Salmonella and mock treated segments showed that the response-time and type of response to Salmonella was different in all three pigs. This plasticity allowed us to extract a comprehensive set of differentially expressed genes from inter-animal comparisons at 2 and 4 hours. Pathway analysis indicated that many of these genes play a role in induction and/or tempering the inflammatory response in the intestine. Among them a set of transcription factors/regulators known to be involved in regulation of inflammation, but also factors/regulators for which involvement was not expected. Nine out of twenty compounds of natural origin, which according to literature had the potential to modulate the activity of these factors/regulators, were able to stimulate or inhibit a Salmonella-induced mRNA response of inflammatory-reporter genes IL8 and/or nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha in cultured intestinal porcine epithelial cells.ConclusionsWe describe a set of transcription factors/regulators possibly involved in regulation of “very early” immune mechanism which determines the inflammatory status of the intestine later on. In addition, we show that these mechanisms may be modulated by chemical substances of natural origin.

【 授权许可】

CC BY   
© Hulst et al.; licensee BioMed Central Ltd. 2013