Production of Cytokines by Monocytes, Epithelial and Endothelial Cells Activated by Streptococcus Bovis

The Role of Infectious Agents in Colorectal Carcinogenesis

“…Fifty percent of the rats receiving WEA developed colonic adenomas, whereas no tumour was detected in the other groups. It is noteworthy to mention that normal rats did not develop hyperplastic colonic crypts upon treatment with S. bovis suspension, implying that S. bovis proteins are involved in promoting rather than initiating oncogenesis (Ellmerich et al, 2000b). Similar results were obtained by Biarc et al, (2004) who also reported that a purified form of S. bovis WEA (S300 fraction) is even more potent inducer of neoplastic progression than WEA or the intact bacteria.…”

Streptococcus bovis/gallolyticus Induce the Development of Colorectal Cancer

“…It has been suggested that alterations in local conditions and disruption of capillary channels at the site of neoplasm allowed S. bovis/gallolyticus to proliferate and gain entry into blood stream (Biarc et al, 2004;Ellmerich et al, 2000a;Nguyen et al, 2006). The local action of cytokines or of chemical mediators able to promote vasodilatation and the enhancement of capillary permeability, may support the bacterial entry at tumor sites, and increase bacterial adherence to various cells (Biarc et al, 2004;Ellmerich et al, 2000b).…”

“…Fifteen days (week 4) after the last injection of the carcinogen, the rats received, by gavage twice per week during 5 weeks, either S. bovis (10 10 bacteria) or wall-extracted antigens (WEAs) (100 µg). One week after the last gavage (week 10), it was found that administration of either S. bovis or its antigens promoted the progression of preneoplastic lesions into neoplastic lesions through the increased formation of hyperproliferative aberrant colonic crypts, which enhanced the expression of proliferation markers and increased the production of IL-8 in the colonic mucosa (Biarc et al, 2004;Ellmerich et al, 2000b). Therefore, this study suggests that S. bovis/gallolyticus bacteria act as potential promoters of early preneoplastic lesions in the colon of rats, and their cell wall proteins are more potent inducers of neoplastic transformation than the intact bacteria.…”

“…Earlier it was found that the production of inflammatory cytokines in response to S. bovis/gallolyticus, such as TNF-α, IL-1ß and IL-6, and the chemokine IL-8, were found to contribute to the normal defense mechanisms of the host (Ellmerich et al, 2000b;Travers & Rosen, 1997) leading to the formation of nitric oxide and free radicals such as superoxide, peroxynitrites, hydroxyl radicals as well as alkylperoxy radicals (Nguyen et al, 2006;Ohshima & Bartsch, 1994). Owing to their potent mutagenicity, all these molecular species can contribute to the neoplastic processes by modifying cellular DNA.…”

“…Owing to their potent mutagenicity, all these molecular species can contribute to the neoplastic processes by modifying cellular DNA. On the other hand, in the colonic mucosa, the production of angiogenic factors, such as IL-8, triggered by S. bovis/gallolyticus antigens may also favor the progression of colon carcinogenesis (Eisma et al, 1999;Ellmerich et al, 2000b;Norrby, 1996). This resembles H. pylori infection for the development of chronic inflammation in the gastric mucosa (Dixon et al, 1996); therefore, it seems that chronic infection and subsequent chronic inflammation are responsible for the maintenance and development of pre-existing neoplastic lesions (Shacter & Weitzman, 2002).…”