TAILIEUCHUNG - Báo cáo y học: "Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts"

Tham khảo luận văn - đề án 'báo cáo y học: "effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts"', luận văn - báo cáo phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | Asp et al. Journal of Inflammation 2011 8 25 http content 8 1 25 JOURNAL OF INFLAMMATION RESEARCH Open Access Effects of pro-inflammatory cytokines on expression of kynurenine pathway enzymes in human dermal fibroblasts 1 112 3 Linnéa Asp Anne-Sofie Johansson Amandeep Mann Bjorn Owe-Larsson Ewa M Urbanska Tomasz Kocki Magdalena Kegel5 Goran Engberg5 Gabriella BS Lundkvist1 and Hakan Karlsson1 Abstract Background The kynurenine pathway KP is the main route of tryptophan degradation in the human body and generates several neuroactive and immunomodulatory metabolites. Altered levels of KP-metabolites have been observed in neuropsychiatric and neurodegenerative disorders as well as in patients with affective disorders. The purpose of the present study was to investigate if skin derived human fibroblasts are useful for studies of expression of enzymes in the KP. Methods Fibroblast cultures were established from cutaneous biopsies taken from the arm of consenting volunteers. Such cultures were subsequently treated with interferon IFN -y 200 U ml and or tumor necrosis factor TNF -a 100 U ml for 48 hours in serum-free medium. Levels of transcripts encoding different enzymes were determined by real-time PCR and levels of kynurenic acid KYNA were determined by HPLC. Results At base-line all cultures harbored detectable levels of transcripts encoding KP enzymes albeit with considerable variation across individuals. Following cytokine treatment considerable changes in many of the transcripts investigated were observed. For example increases in the abundance of transcripts encoding indoleamine 2 3-dioxygenase kynureninase or 3-hydroxyanthranilic acid oxygenase and decreases in the levels of transcripts encoding tryptophan 2 3-dioxygenase kynurenine aminotransferases or quinolinic acid phosphoribosyltransferase were observed following IFN-y and TNF-a treatment. Finally the fibroblast cultures released detectable levels of KYNA in the cell culture

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