Wanphen Wannapapho. Induction of inflammatory cytokine expression in epithelial cells and cultured cholangiocarcinoma cells in response to opisthorchis viverrini antigen stimulation . Master's Degree(Microbiology). Mahidol University. : Mahidol University, 2004.
Induction of inflammatory cytokine expression in epithelial cells and cultured cholangiocarcinoma cells in response to opisthorchis viverrini antigen stimulation
Abstract:
Cholangiocarcinoma (CCA), a bile-duct epithelial cancer, is a serious public
health problem, particularly in the northeastern part of Thailand. There are currently
no effective means of diagnosis or treatment for this disease. It is known that
infection with liver fluke, Opisthorchis viverrini, is associated with an increased risk
of developing CCA. Although O. viverrini infection is a known causal factor for CCA
development, the mechanism by which these worms involve in carcinogenesis is
unclear. Furthermore, chronic infection and inflammation are also risk factors for the
development of CCA. However, the link between inflammation and carcinogenesis is
still obscure. The objective of this study was to evaluate the inflammatory cytokine
production that occurs in response to O. viverrini stimulation. We investigated the in
vitro response of cultured human epithelial and CCA cell lines to O. viverrini antigen
stimulation. Reverse transcription-polymerase chain reaction (RT-PCR) and enzymelinked
immunosorbent assay (ELISA) were applied to evaluate the mRNA expression
and protein level of cytokine in the spent culture fluid, respectively.
The results showed that human CCA cell lines constitutively expressed several
pro-inflammatory (IL-1α, IL-1β, IL-6, IL-8) and anti-inflammatory (TGF-α, TGF-β1)
cytokines. Subsequently, human CCA cells were stimulated with O. viverrini
antigens, there were only small changes in the cytokine mRNA expression. By
contrast, a significant increase of both pro-inflammatory (IL-1β, IL-6, IL-8) and also
anti-inflammatory (TGF-β1) cytokine proteins was observed. Similar results were
observed when the lung epithelial (A549) cell line was subsequently used for
comparison. By contrast, a significant decrease in production of IL-8 by the colon
epithelial (Caco-2) cell line was observed after stimulated with O. viverrini antigens.
In conclusion, although different human epithelial cell lines could be stimulated with
the same O. viverrini antigen preparations, the amount and overall pattern of the
inflammatory cytokine production in response to parasite stimulation varied from one
cell line to another.