BMC Cancer | |
Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas | |
Melissa Kang1  Patrick Edmundson1  Felix Araujo-Perez1  Amber N McCoy1  Joseph Galanko1  Temitope O Keku1  | |
[1] Center for Gastrointestinal Biology and Disease, University of North Carolina, 103 Mason Farm Road, 7340 Medical Biomolecular Research Building, CB # 7032, 27599-7032, Chapel Hill, NC, USA | |
关键词: Limulus amebocyte lysate; Adenoma; Colonic neoplasm; Inflammatory cytokines; Endotoxin; | |
Others : 1079899 DOI : 10.1186/1471-2407-13-91 |
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received in 2012-08-20, accepted in 2013-02-18, 发布年份 2013 | |
【 摘 要 】
Background
Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas.
Methods
This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa.
Results
Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6).
Conclusions
These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of colorectal adenomas.
【 授权许可】
2013 Kang et al; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61(2):69-90.
- [2]Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J: Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 2012, 22(2):292-298.
- [3]Scanlan PD, Shanahan F, Clune Y, Collins JK, O'Sullivan GC, O'Riordan M, Holmes E, Wang Y, Marchesi JR: Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol 2008, 10(3):789-798.
- [4]Sobhani I, Tap J, Roudot-Thoraval F, Roperch JP, Letulle S, Langella P, Corthier G, Tran Van Nhieu J, Furet JP: Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One 2011, 6(1):e16393.
- [5]Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, Jia W, Cai S, Zhao L: Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 2012, 6(2):320-329.
- [6]Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM: Enterotypes of the human gut microbiome. Nature 2011, 473(7346):174-180.
- [7]Li Y, Kundu P, Seow SW, de Matos CT, Aronsson L, Chin KC, Karre K, Pettersson S, Greicius G: Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APCMin/+ mice. Carcinogenesis 2012, 33(6):1231-1238.
- [8]Tlaskalova-Hogenova H, Stepankova R, Hudcovic T, Tuckova L, Cukrowska B, Lodinova-Zadnikova R, Kozakova H, Rossmann P, Bartova J, Sokol D: Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 2004, 93(2–3):97-108.
- [9]Vannucci L, Stepankova R, Kozakova H, Fiserova A, Rossmann P, Tlaskalova-Hogenova H: Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int J Oncol 2008, 32(3):609-617.
- [10]Tjalsma H, Boleij A, Marchesi JR, Dutilh BE: A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat Rev Microbiol 2012, 10(8):575-582.
- [11]Sears CL, Pardoll DM: Perspective: alpha-bugs, their microbial partners, and the link to colon cancer. J Infect Dis 2011, 203(3):306-311.
- [12]Abdulamir AS, Hafidh RR, Abu Bakar F: The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J Exp Clin Cancer Res 2011, 30:11. BioMed Central Full Text
- [13]Sanapareddy N, Legge RM, Jovov B, McCoy A, Burcal L, Araujo-Perez F, Randall TA, Galanko J, Benson A, Sandler RS: Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans. ISME J 2012, 6(10):1858-1868.
- [14]Shen XJ, Rawls JF, Randall T, Burcal L, Mpande CN, Jenkins N, Jovov B, Abdo Z, Sandler RS, Keku TO: Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut microbes 2010, 1(3):138-147.
- [15]Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008, 57(6):1470-1481.
- [16]Cani PD, Neyrinck AM, Fava F, Knauf C, Burcelin RG, Tuohy KM, Gibson GR, Delzenne NM: Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia 2007, 50(11):2374-2383.
- [17]Atreya R, Neurath MF: Signaling molecules: the pathogenic role of the IL-6/STAT-3 trans signaling pathway in intestinal inflammation and in colonic cancer. Curr Drug Targets 2008, 9(5):369-374.
- [18]Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA, Oft M: IL-23 promotes tumour incidence and growth. Nature 2006, 442(7101):461-465.
- [19]Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M: IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 2004, 118(3):285-296.
- [20]Puppa MJ, White JP, Sato S, Cairns M, Baynes JW, Carson JA: Gut barrier dysfunction in the Apc(Min/+) mouse model of colon cancer cachexia. Biochim Biophys Acta 2011, 1812(12):1601-1606.
- [21]Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS: Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 2008, 68(1):323-328.
- [22]Jovov B, Araujo-Perez F, Sigel CS, Stratford JK, McCoy AN, Yeh JJ, Keku T: Differential gene expression between African American and European American colorectal cancer patients. PLoS One 2012, 7(1):e30168.
- [23]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods (San Diego, Calif) 2001, 25(4):402-408.
- [24]Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 2001, 29(9):e45.
- [25]Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc, Ser B (Methodological) 1995, 57(1):289-300.
- [26]Pendyala S, Walker JM, Holt PR: A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 2012, 142(5):1100-1101. e1102
- [27]Lee KK, Yum KS: Association of endotoxins and colon polyp: a case–control study. J Korean Med Sci 2012, 27(9):1062-1065.
- [28]Im E, Riegler FM, Pothoulakis C, Rhee SH: Elevated lipopolysaccharide in the colon evokes intestinal inflammation, aggravated in immune modulator-impaired mice. Am J Physiol 2012, 303(4):G490-497.
- [29]Cui G, Yuan A, Goll R, Olsen T, Husebekk A, Vonen B, Florholmen J: Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma-carcinoma sequence. Cancer Immunol Immunother 2007, 56(12):1993-2001.
- [30]Contasta I, Berghella AM, Pellegrini P, Adorno D: Passage from normal mucosa to adenoma and colon cancer: alteration of normal sCD30 mechanisms regulating TH1/TH2 cell functions. Cancer Biother Radiopharm 2003, 18(4):549-557.
- [31]Murugaiyan G, Saha B: Protumor vs antitumor functions of IL-17. J Immunol 2009, 183(7):4169-4175.
- [32]Su X, Ye J, Hsueh EC, Zhang Y, Hoft DF, Peng G: Tumor microenvironments direct the recruitment and expansion of human Th17 cells. J Immunol 2009, 184(3):1630-1641.
- [33]Keku TO, Sandler RS, Simmons JG, Galanko J, Woosley JT, Proffitt M, Omofoye O, McDoom M, Lund PK: Local IGFBP-3 mRNA expression, apoptosis and risk of colorectal adenomas. BMC Cancer 2008, 8:143. BioMed Central Full Text
- [34]Ellmerich S, Scholler M, Duranton B, Gosse F, Galluser M, Klein JP, Raul F: Promotion of intestinal carcinogenesis by streptococcus bovis. Carcinogenesis 2000, 21(4):753-756.
- [35]Martin C, Connelly A, Keku TO, Mountcastle SB, Galanko J, Woosley JT, Schliebe B, Lund PK, Sandler RS: Nonsteroidal anti-inflammatory drugs, apoptosis, and colorectal adenomas. Gastroenterology 2002, 123(6):1770-1777.
- [36]Keku TO, Lund PK, Galanko J, Simmons JG, Woosley JT, Sandler RS: Insulin resistance, apoptosis, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 2005, 14(9):2076-2081.
- [37]Carroll RE, Benya RV, Turgeon DK, Vareed S, Neuman M, Rodriguez L, Kakarala M, Carpenter PM, McLaren C, Meyskens FL Jr: Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011, 4(3):354-364.
- [38]Thompson PA, Wertheim BC, Zell JA, Chen WP, McLaren CE, LaFleur BJ, Meyskens FL, Gerner EW: Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma. Gastroenterology 2010, 139(3):797-805. 805 e791
- [39]Barnes CJ, Hamby-Mason RL, Hardman WE, Cameron IL, Speeg KV, Lee M: Effect of aspirin on prostaglandin E2 formation and transforming growth factor alpha expression in human rectal mucosa from individuals with a history of adenomatous polyps of the colon. Cancer Epidemiol Biomarkers Prev 1999, 8(4 Pt 1):311-315.
- [40]Ponz De Leon M, Roncucci L, Di Donato P, Tassi L, Smerieri O, Amorico MG, Malagoli G, De Maria D, Antonioli A, Chahin NJ: Pattern of epithelial cell proliferation in colorectal mucosa of normal subjects and of patients with adenomatous polyps or cancer of the large bowel. Cancer Res 1988, 48(14):4121-4126.
- [41]Momozawa Y, Deffontaine V, Louis E, Medrano JF: Characterization of bacteria in biopsies of colon and stools by high throughput sequencing of the V2 region of bacterial 16S rRNA gene in human. PLoS One 2011, 6(2):e16952.
- [42]Monte SV, Caruana JA, Ghanim H, Sia CL, Korzeniewski K, Schentag JJ, Dandona P: Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus. Surgery 2012, 151(4):587-593.
- [43]Assimakopoulos SF, Tsamandas AC, Tsiaoussis GI, Karatza E, Triantos C, Vagianos CE, Spiliopoulou I, Kaltezioti V, Charonis A, Nikolopoulou VN: Altered intestinal tight junctions' expression in patients with liver cirrhosis: a pathogenetic mechanism of intestinal hyperpermeability. Eur J Clin Invest 2012, 42(4):439-446.
- [44]Lira FS, Rosa JC, Pimentel GD, Souza HA, Caperuto EC, Carnevali LC Jr, Seelaender M, Damaso AR, Oyama LM, de Mello MT: Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects. Lipids Health Dis 2010, 9:82. BioMed Central Full Text