Local production of chemokines and prostaglandin E2 in the acute, chronic and recovery phase of murine experimental colitis.

Department of Integrative Pharmacology, AstraZeneca R&D Mölndal, GI Biology, SE-431 83, Sweden.
Cytokine (Impact Factor: 2.87). 10/2006; 35(5-6):275-83. DOI: 10.1016/j.cyto.2006.09.007
Source: PubMed

ABSTRACT Increased levels of chemokines and prostaglandins have been reported in patients with inflammatory bowel disease, although their changes during disease development are less understood. The aim of this study was to investigate the local production of nine selected chemokines and prostaglandin E(2) (PGE(2)) to elucidate their role in colitis progression in BALB/c and C57BL/6 mice exposed to dextran sulphate sodium. The acute inflammation in both strains was accompanied by a significant up-regulation of CXCL1, CXCL2/3, CXCL10, CCL2, CCL4 and CCL22 and a downregulation of PGE(2). In the recovery phase in BALB/c, one-week post-DSS, PGE(2) levels were significantly increased with a concomitant downregulation of CXCL1, CXCL2/3, CXCL10, CCL2, and CCL4. In contrast, in C57BL/6 mice CXCL1, CXCL2/3, CXCL10, CCL2, CCL3 and CCL4 production remained high during the chronic phase, without any up-regulation of PGE(2). In addition, CCL5 was significantly increased at d26 and 33 compared to d5. Interestingly, the number of macrophages was significantly increased during the acute phase, whereas T cells were significantly increased in both the acute and chronic phase in C57BL/6 mice. Thus, our results show that chemokines are produced in a dynamic manner during colitis progression.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The mouse secretory phospholipase A2 group IIA (sPLA2-IIA) gene Pla2g2a has been identified as a susceptibility gene for cancer of the small and large intestine. Interestingly, unlike most previously identified tumor susceptibility genes, Pla2g2a does not behave like a classical oncogene or tumor suppressor gene. Hence, identification of its biological functions in tumor development may shed new light on general mechanisms that modulate colon cancer risk. So far, sPLA2-IIA has been proposed to play a role in anti-bacterial defense, inflammation and eicosanoid generation, in clearance of apoptotic cells, and in the Wnt signaling pathway. More recently, comparison of RNA expression profiles of colon from Pla2g2a-transgenic to Pla2g2a-deficient mice confirmed and even extended sPLA2-IIA's diverse biological effects. In this review we aim to summarize current knowledge about the various links of sPLA2-IIA to cancer of the gastro-intestinal tract, and propose several models to illustrate its putative biological effects on tumor development.
    Frontiers in Bioscience 05/2008; Volume(13):4144. DOI:10.2741/2998 · 4.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phellinus linteus is a herb used in traditional Asian medicine to treat stomachache, inflammation, and tumors. Recent studies show that the extract of P. linteus has anti-inflammatory and antitumor activities. However, P. linteus extract has limitation of high cost and limited availability because of supply shortage. Here, we grew P. linteus on germinated brown rice to address the issue of supply shortage and investigated anti-inflammatory effect in vivo as well as in vitro. Phellinus linteus grown on germinated brown rice (PBR) were extracted using filtration steps, which included γ-aminobutyric acid (GABA). The PBR (200mg/kg/day, 500mg/kg/day) was applied into the mouse model of dextran sodium sulfate (DSS)-induced colitis and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. We used sulfasalazine as a reference drug. In addition, mechanism related to anti-inflammatory was investigated by western blotting. In the mouse model of DSS-induced colitis, PBR ameliorated the pathological characteristics of colitis such as shortening of colon length and improved the disease activity index score. In addition, we showed that PBR reduced the expression of nuclear factor-kappa B (NF-κB) in colitis. Western blotting showed that PBR decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) proteins. Further, PBR treatment reduced the expression of mitogen-activated protein kinases (MAPKs) (e.g., extracellular signal-regulated protein kinase (ERK) and p38) in the mouse model of DSS-induced colitis. Treatment of RAW 264.7 macrophages with a combination of PBR and LPS showed a significant concentration-dependent inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) production. In addition, we determined the ability of PBR to reduce the iNOS and tumor necrosis factor (TNF)-α expression. PBR inhibited the expression of iNOS, NF-κB, and Cox-2 proteins in LPS-stimulated RAW264.7 macrophages. This study presents the potential use of PBR as a drug candidate against colitis.
    Journal of ethnopharmacology 02/2014; DOI:10.1016/j.jep.2013.12.059 · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The vitamin A metabolite retinoic acid (RA) has been reported to suppress Th1 responses and enhance Th2 responses. Here we investigated whether differences in vitamin A metabolism could underlie the differences between C57BL/6 and BALB/c mice, which are reportedly seen as Th1 and Th2 responders, respectively. BALB/c mice were shown to have higher intestinal epithelial expression of RALDH1, and, consequently, higher RALDH activity in MLN-DCs, leading to an increased ability to induce IgA class switching in B cells. Furthermore, within BALB/c mice, induction of IgA secretion as well as increased accumulation of regulatory T (Treg) cells in the intestinal lamina propria was observed. Additionally, as BALB/c mice are more resistant to Dextran Sulphate Sodium (DSS)-induced colitis, mice that lacked vitamin A in their diet had a more severe form of DSS-induced colitis compared to control mice. Therefore, the level of RA production and consequently the degree of RA-mediated signaling is crucial for the efficiency of the mucosal immune system.This article is protected by copyright. All rights reserved
    European Journal of Immunology 01/2015; 45(1). DOI:10.1002/eji.201343340 · 4.52 Impact Factor


Available from
Jun 5, 2014