Article

A cytokine-mediated link between innate immunity, inflammation, and cancer.

Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Journal of Clinical Investigation (Impact Factor: 13.77). 06/2007; 117(5):1175-83. DOI: 10.1172/JCI31537
Source: PubMed

ABSTRACT It has been established that cancer can be promoted and/or exacerbated by inflammation and infections. Indeed, chronic inflammation orchestrates a tumor-supporting microenvironment that is an indispensable participant in the neoplastic process. The mechanisms that link infection, innate immunity, inflammation, and cancer are being unraveled at a fast pace. Important components in this linkage are the cytokines produced by activated innate immune cells that stimulate tumor growth and progression. In addition, soluble mediators produced by cancer cells recruit and activate inflammatory cells, which further stimulate tumor progression. However, inflammatory cells also produce cytokines that can limit tumor growth. Here we provide an overview of the current understanding of the role of inflammation-induced cytokines in tumor initiation, promotion, and progression.

1 Follower
 · 
152 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to determine the anti-inflammatory effects of preventive administration of a probiotic strain Lactobacillus plantarum LS/07 CCM7766 alone or in combination with prebiotic inulin or with flax-seed oil in the gut of rats, which developed chronic inflammation following administration of the pro-carcinogen N,N-dimethylhydrazine (DMH). After 28 weeks administration of probiotic/prebiotic-containing diet, rats were killed and their colons were examined by immunohistological criteria, whereas cytokines were determined in the jejunal mucosa. Application of DMH had a strong stimulatory effect on the production of pro-inflammatory cytokines IL-2, IL-6, IL-17, and TNF-α, expression of pro-inflammatory mediators NF-κB, COX-2 and iNOS and caused depletion of goblet cells. Supplementing the diet with L. plantarum and its combination with the prebiotic abolished DMH-induced inflammatory process in the jejunal mucosa by inhibiting the production of pro-inflammatory cytokines and by stimulation of anti-inflammatory IL-10 cytokine synthesis, whereas concentration of TGF-β1 was not influenced significantly. Diet prevented a decrease in goblet cell numbers but numbers of mast cells were lowered only moderately. However, combined treatment of rats with L. plantarum and flax-seed oil had no significant effect on the parameters examined, except for decreased expression of NF-κB, in comparison with the negative control. Results indicate that the preventive administration of probiotic L. plantarum LS/07 CCM7766 alone or in combination with prebiotic inulin to rats with DMH-induced chronic inflammation can reduce inflammatory process in the jejunal and colon mucosas, probably indirectly, and involves down-regulation of synthesis of pro-inflammatory cytokines and suppression of NF-κB activity in mucosal cells.
    International Immunopharmacology 12/2014; 24(2). DOI:10.1016/j.intimp.2014.12.022 · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ganoderma lucidum is a popular medicinal mushroom with anti-inflammatory potential. In the present study, the aim was to determine the anti-inflammatory effect and mode of action of G. lucidum grown on germinated brown rice (GLBR) in a mouse model of colitis. It was shown that GLBR suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages and decreased the expression of COX-2, TNF-a, iNOS, IL-1b, IL-6, and IL-10 mRNAs. GLBR also inhibited activation of p38, ERK, JNK, MAPKs, and nuclear factor kappa-B (NF-jB). In a mouse model of colitis, colonic mucosal injury was evaluated using macroscopic, biochemical, and histopathological testing. Disease activity index (DAI), macroscopic score, and histological score significantly decreased upon GLBR treatment. Moreover, immunofluorescence studies indicated that DSS activates nuclear translocation of NF-kB in colon tissue, which is attenuated by GLBR extract. These findings suggest that GLBR is protective against colitis via inhibition of MAPK phosphorylation and NF-kB activation.
    Phytochemistry 11/2014; DOI:10.1016/j.phytochem.2014.10.019 · 3.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glioma cells release cytokines to stimulate inflammation that facilitates cell proliferation. Here, we show that Lipopolysaccharide (LPS) treatment could induce glioma cells to proliferate and this process was dependent on nucleotide receptor activation as well as interleukin-8 (IL-8/CXCL8) secretion. We observed that extracellular nucleotides controlled IL-8/CXCL8 and monocyte chemoattractant protein 1 (MCP-1/CCL2) release by U251MG and U87MG human glioma cell lines via P2X7 and P2Y6 receptor activation. The LPS-induced release of these cytokines was also modulated by purinergic receptor activation since IL-8 and MCP-1 release was decreased by the nucleotide scavenger apyrase as well as by the pharmacological P2Y6 receptor antagonists suramin and MRS2578. In agreement with these observations, the knockdown of P2Y6 expression decreased LPS-induced IL-8 release as well as the spontaneous release of IL-8 and MCP-1, suggesting an endogenous basal release of nucleotides. Moreover, high millimolar concentrations of ATP increased IL-8 and MCP-1 release by the glioma cells stimulated with suboptimal LPS concentration which were blocked by P2X7 and P2Y6 antagonists. Altogether, these data suggest that extracellular nucleotides control glioma growth via P2 receptor-dependent IL-8 and MCP-1 secretions. Copyright © 2014 Elsevier B.V. All rights reserved.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 10/2014; 1852(1):120-130. DOI:10.1016/j.bbadis.2014.10.014 · 5.09 Impact Factor

Preview

Download
2 Downloads
Available from