| Summary: | 碩士 === 國立嘉義大學 === 微生物免疫與生物藥學系研究所 === 103 === Candida species is the most common opportunistic fungal pathogen of human. Candida albicans, one of Candida species, is a frequently fatal systemic pathogen. Compare the common body fluid of human including urine, sputum, blood and others, the Candida strains are isolated mostly from urine; therefore, bladder epithelia layer is an important barrier for defense of Candida strains’ invasion. So in this study, the host cellular response of urothelium infected by C. albicans was investigated. Currently, we found that C. albicans caused the urothelial morphology change, cell damage, cell de-attachment and inflammatory response including cyclooxygenase-2 (COX-2) gene and protein expression, prostaglandin E2 accumulation and interleukin-8 gene expression. Then the molecular mechanism of C. albicans-induced urothelial COX-2 gene expression was studied. The pathways potentially related to COX-2 expression were examined by Western blot. We observed the phosphorylation of ERK1/2, p38, and JNK were all increased after C. albicans infection for 12 h. The C. albicans-induced COX-2 protein expression was inhibited by the specific inhibitor of ERK and p38 (U0126 and SB203580), but not by the JNK inhibitor SP600125. We also observed increased amount of phosphorylation of RSK that is the mutual downstream molecule of ERK1/2 and p38. Furthermore, phosphorylation of RSK protein expression is decreased by the treatment of ERK or p38 inhibitors. Base on the data, it suggests that the urothelial COX-2 gene is induced majorly though ERK/p38-RSK pathway by C. albicans infection. And we found that transcription factor cAMP response element-binding protein-1 (CREB-1) was increased in binding to COX-2 gene promoter. Using receptor inhibitors including Toll-like receptors (TLRs)-MyD88 inhibitor (ST2825), Dectin-syk receptor inhibitor (syk inhibitor) and epidermal growth factor receptor (EGFR) inhibitor (PD168393) to identify which was the main receptor for C. albicans-induced COX-2 expression. We found that EGFR played an important mediator to activate ERK/p38-RSK pathway and induce COX-2 expression.
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