Systemic administration of the chemokine macrophage inflammatory protein 1 α exacerbates inflammatory bowel disease in a mouse model

Pender, S. L.-F.; Chance, V.; Whiting, C. V.; Buckley, M.; Edwards, M.; Pettipher, R.; MacDonald, T. T.
August 2005
Gut;Aug2005, Vol. 54 Issue 8, p1114
Academic Journal
Introduction: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1α (MIP-1α) exacerbates colitis in a mouse model. Methods: Colitis was induced in Balb/c mice using trinitrobenzene sulfonic acid (TNBS). Starting four days later, animals received daily intraperitoneal injections of recombinant MIP-1α. On day 7, mice were killed and pieces of colon taken for immunohistology and polymerase chain reaction analysis. The direct effects of MIP-1α on mucosal T cells and fibroblasts in vitro were also investigated. Results: Systemic administration of MIP-1α markedly enhanced colitis with mice developing large transmural ulcers filled with granulation tissue. Treatment resulted in increased numbers of CD4 cells infiltrating the colonic lamina propria, increased interferon γ (IFN-γ) levels, and increased transcripts for tumour necrosis factor α (TNF-α) and matrix metalloproteinase 3 (MMP3). Isolated lamina propria lymphocytes from mice with TNBS colitis contained increased numbers of IFN-γ and TNF-α transcripts when stimulated with MIP-1α in vitro. Colonic lamina propria fibroblasts also responded to M1P-1α with increased proliferation and decreased collagen 1 synthesis but fibroblast proliferation was not seen in vivo. Conclusions: These experiments show that increasing serum concentrations of a chemokine, MIP-1α, exacerbates immune mediated colitis. The effect seems to be due to the ability of MIP-1α to boost Th1 responses in the gut wall. Our findings also suggest a potential pathway by which peripheral infections can exacerbate inflammatory bowel disease.


Related Articles

  • Inhibition of Histone Deacetylases in Inflammatory Bowel Diseases. Glauben, Rainer; Siegmund, Britta // Molecular Medicine;May/Jun2011, Vol. 17 Issue 5/6, p426 

    This review, comprised of our own data and that of others, provides a summary overview of histone deacetylase (HDAC) inhibition on intestinal inflammation as well as inflammation-mediated carcinogenesis. Experimental colitis in mice represents an excellent in vivo model to define the specific...

  • Mucosal immunology: Don't forget our fungal friends. Minton, Kirsty // Nature Reviews Immunology;Jul2012, Vol. 12 Issue 7, p476 

    The article presents the study that investigates the importance of commensal fungi in the immune system. Researchers studied and analyzed the interactions of fungi inside the intestinal immune system using a mouse model and they found that the presence of fungi in the gut are associated with...

  • Role of interleukin 15 in colitis induced by dextran sulphate sodium in mice. Yoshihara, K.; Yajima, Toshiki; Kubo, C.; Yoshikai, Y. // Gut;Mar2006, Vol. 55 Issue 3, p334 

    Background and aims: Interleukin (IL)-15 is a member of the IL-2 family, stimulating dendritic cells, natural killer (NK) cells, NK T cells and memory CD8+ T cells. IL-15 levels were elevated in the intestinal mucosa of inflammatory bowel diseases. Here we investigated the involvement of IL-15...

  • The IL23 axis plays a key role in the pathogenesis of IBD. McGovern, Dermot; Powrie, Fiona // Gut;Oct2007, Vol. 56 Issue 10, p1333 

    Exciting new results from a genetic study in humans and functional studies in mice have pinpointed interleukin 23 (IL23) and its receptor as a key pathway in the pathogenesis of inflammatory bowel disease (IBD). These findings reveal a hitherto unappreciated role for the IL23 axis in intestinal...

  • Hyaluronan Synthase 3 Null Mice Exhibit Decreased Intestinal Inflammation and Tissue Damage in the DSS-Induced Colitis Model. Kessler, Sean P.; Obery, Dana R.; de la Motte, Carol // International Journal of Cell Biology;9/10/2015, Vol. 2015, p1 

    Hyaluronan (HA) overproduction is a hallmark of multiple inflammatory diseases, including inflammatory bowel disease (IBD). Hyaluronan can act as a leukocyte recruitment molecule and in the most common mouse model of intestinal inflammation, the chemically induced dextran sodium sulfate (DSS)...

  • Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice. K. Inagaki-Ohara; A. Sasaki; G. Matsuzaki; I. Ikeda; M. Hotokezaka; K. Chijiiwa; M. Kubo; H. Yoshida; Y. Nawa; A. Yoshimura // Gut;Feb2006, Vol. 55 Issue 2, p212 

    Background and aims: Imbalance between pro- and anti-inflammatory cytokines produced by intestinal T cells induces inflammatory bowel diseases (IBD). However, the importance of regulation of cytokine signalling in IBD has not been fully clarified. We have demonstrated that suppressor of cytokine...

  • High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice. Lu, Peng; Bar-Yoseph, Fabiana; Levi, Liora; Lifshitz, Yael; Witte-Bouma, Janneke; de Bruijn, Adrianus C. J. M.; Korteland-van Male, Anita M.; van Goudoever, Johannes B.; Renes, Ingrid B. // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Background: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha’-palmitate), the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2...

  • Contribution of bone marrow-derived cells to the pro-inflammatory effects of protease-activated receptor-2 in colitis. Hyun, Eric; Andrade-Gordon, Patricia; Steinhoff, Martin; Beck, Paul; Vergnolle, Nathalie // Inflammation Research;Sep2010, Vol. 59 Issue 9, p699 

    Our aim was to determine the contribution of proteinase-activated receptor-2 (PAR2)-expressing bone marrow-derived cells on the development of colonic inflammation. Chimeric mice were generated by injecting bone marrow cells from wildtype (PAR) or PAR2 knockout mice (PAR) into irradiated PAR or...

  • RAGE and ICAM-1 differentially control leukocyte recruitment during acute inflammation in a stimulus-dependent manner.  // BMC Immunology;2011, Vol. 12 Issue 1, p56 

    The article presents information on the study of stimulus-dependent role of receptor for advanced glycation endproducts (RAGE) on leucocyte recruitment during inflammation. The study was conducted using intravital microscopy. It was demonstrated that not ICAM-1 mice, but RAGE contributes to...


Read the Article


Sign out of this library

Other Topics