細胞激素(cytokine)，為內分泌系統的一員，在人體中扮演著相當重要的角色，其功能主要在於免疫系統方面，舉凡血球( T cell、B cell、monocyte…etc )的分化、生成及促進免疫系統對抗外來病原體入侵的反應，皆需要細胞激素的作用，常見的有: IFN-γ、TNF-α及IL-10等。
　　有數種現今已知的細胞激素被發現與IL-10 有著相當比例的胺基酸相似性，而被歸類為同一族。此一IL-10 family包括IL-19、IL-20、IL-22[IL-10-related T-cell-derived inducible factor(IL-TIF)]、IL-24 [melanoma differentiation-associated antigen 7(MDA-7)]和IL-26 (AK155) 。經由各自訊息傳導及轉錄因子的活化，各自引起不同的生物作用，例如IL-22/IL-TIF會造成肝細胞的急性期反應；而IL-20則會導致角質細胞的過度增生。至於IL-24則被認為與癌細胞的生長有關，其他如IL-19、IL-26的功能至目前為止仍沒有清楚的了解。此一家族的成員中以IL-10、IL-19、IL-20、IL-24皆位於第一對染色體的一段200kb序列中，而IL-22、IL-26則被發現位於第12對染色體上。
　　Interleukin-19(IL-19)在2000年首次被發現，是由被LPS ( lipopolysaccharide )所刺激後的monocyte表現出來的，經過比對之後發現和IL-10在胺基酸序列上有21%的相同性( homologous )及37%的相似性( similaty )而被歸屬於IL-10 family的一員，且在coding region上皆以5個exon、4個intron的結構為主。IL-10在先前的研究中被發現會抑制monocyte、T cell和B cell等免疫細胞的活化及其他細胞激素的產生，如IFN-γ，而被認為主要的功能為抗發炎的作用。此外，在IL-10 promoter的研究中也有相當多的報告指出，單一核酸的多型性( single nucleotide polymorphisms, SNP )會對IL-10的表現造成影響，而導致免疫系統的不正常，多與自體免疫疾病有關，如SLE、RA及MS等。
　　因此，本實驗室便針對IL-10 family 中的IL-19進行其promoter region的研究。IL-19的coding region有1031bp可表現出177個胺基酸。在經由5’RACE實驗後，我們發現其完整的cDNA序列及其轉譯起始點。而文獻中提到，在IL-19之5’端還有兩段untranslation exon ，且在不同的組織中的長度並不相同。我們從第一個的exon的5’端利用PCR取出一段1.8kb DNA片段，並構築在具有luciferase gene的reporter vector中，再transfect 進入MDCK cell與293 cell中。發現此1.8 kb的片段具有promoter activity。接著再經由series deletion更進一步縮短可能的調控區及EMSA等實驗，而找到了此IL-19的調控相關區域及可能因子。分別在-141~-146的區域可能被HNF-5所結合促進及-42~-51部分之TFIID- MBP的結合，我們也將此段(-141~146)突變來構築一個新的質體來研究這段突變序列對luciferase表現的影響，也得到一個降低的結果。另外我們也從不同的細胞激素刺激中發現GM-CSF(10ng/ml)能增加IL-19 promoter在293 cell的活性。

　　Cytokines are important molecules of hormones. Most of the cytokines are small to medium sized proteins which mediate potent biological effects on most cell types. Originally they are identified as being important in inflammatory processes, the development and maintenance of immune respones and haematopoiesis.
　　A family of interleukin-10 (IL-10)-related cytokines has been emerged which include IL-19, IL-20, IL-22 [IL-10-related T-cell-derived inducible factor (IL-TIF)], IL-24 [melanoma differentiation-associated antigen 7 (MDA-7)] and IL-26 (AK155). Whereas IL-10 is a well-studied pleiotropic immunosuppressive and immun-stimulatory cytokine. It inhibits the production of IL-1, IL-6 and TNF-α. IL-22/IL-TIF can mediate acute-phase response signals in hepatocytes and IL-20 induces the hyperproliferation of keratinocytes. IL-24 is related to the suppression of tumor cell growth. But the function of IL-19 and IL-26 are still unclear. The genes for IL-10, IL-19, IL-20 and IL-24 are found within a 200kb region of chromosome 1 and the two other family members IL-22 and IL-26 are found on chromosome 12.
　　IL-19 was first discoveried in year 2000. It shares 21% amino acid identity with the amino acid sequence of IL-10. In the previous study, it was reported that IL-10 functions as an inhibitor in immune system especial on monocyte、T cell and B cell and the production of cytokines ,such as IFN-γ. The expression of IL-19 mRNA could be induced by LPS and GM-CSF treatment in monocytes. The exon/intron structure of IL-19 is similar to that of the human IL-10 gene, comprising five exons and four introns within the coding region of the IL-19 cDNA. There are at least two distinct IL-19 mRNA species that differ in their 5'-sequences. By 5’RACE experiment, we identified the transcription start site and constructed 5 potential promoter fragments of different length upstream of exon1. We termed these five constructs to PSA、PSB、PSC、PSD、PSE and transfected these plasmid into MDCK and 293 cell lines. The results of luciferase activity showed that the PSE region expressed highest promoter activity in both MDCK and 293 cells. To find the binding protein and binding region of IL-19 promoter, we used EMSA experiment to define the binding sequence between promoter region and transcription factor. The EMSA data proved that a specific region of PSE can bind to some transcription factors contained in the nuclear extract and control the luciferase activity. In the region of nt.-141~-146 and nt.-42~-51, the HNF-5 and TFIID-MBP may bind to the DNA sequence. Furthermore, we mutated the six nucleotide of -141~-146 region in reporter vector. We found the luciferase activity of this mutant decreased 70％ activity compared to the wild type control. When we treated cells with several reagents:LPS﹑TGF-β﹑IFN-γ﹑IL-6﹑GM-CSF. We found that GM-CSF could enhance the IL-19 promoter activity in 293 cell line.

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