Human CSF3 peptide

Background: Periodontitis is the most common chronic inflammatory disease caused by complex interaction between the microbial biofilm and host immune responses. In the present study, high-throughput RNA sequencing was utilized to systemically and precisely identify gene expression profiles and alternative splicing. Methods: The pooled RNAs of 10 gingival tissues from both healthy and periodontitis patients were analyzed by deep sequencing followed by computational annotation and quantification of mRNA structures. Results: The differential expression analysis designated 400 up-regulated genes in periodontitis tissues especially in the pathways of defense/immunity protein, receptor, protease, and signaling molecules. The top 10 most upregulated genes were CSF3, MAFA, CR2, GLDC, SAA1, LBP, MME, MMP3, MME-AS1, and SAA4. The 62 down-regulated genes in periodontitis were mainly cytoskeletal and structural proteins. The top 10 most down-regulated genes were SERPINA12, MT4, H19, KRT2, DSC1, PSORS1C2, KRT27, LCE3C, AQ5, and LCE6A. The differential alternative splicing analysis revealed unique transcription variants in periodontitis tissues. The EDB exon was predominantly included in FN1, while exon 2 was mostly skipped in BCL2A1. Conclusions: These findings using RNA sequencing provide novel insights into the pathogenesis mechanism of periodontitis in terms of gene expression and alternative splicing.

Ex vivo culture of mouse and human skin causes an inflammatory response characterized by production of multiple cytokines. We used ex vivo culture of mouse tail skin specimens to investigate mechanisms of this skin culture-induced inflammatory response. Multiplex assays revealed production of interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during skin culture, and quantitative PCR revealed transcripts for these proteins were also increased. Ex vivo cultures of skin from myeloid differentiation primary response 88 deficient mice (Myd88(-/-)) demonstrated significantly reduced expression of transcripts for the aforementioned cytokines. The same result was observed with skin from interleukin 1 receptor type 1 deficient mice (Il1r1(-/-)). These data suggested the IL-1R1/MyD88 axis is required for the skin culture-induced inflammatory response and led us to investigate the role of IL-1 alpha and IL-1 beta (the ligands for IL-1R1) in this process. Addition of IL-1 alpha neutralizing antibody to skin cultures significantly reduced expression of Cxcl1, Il6 and Csf3. IL-1 beta neutralization did not reduce levels of these transcripts. These studies suggest that IL-1 alpha promotes the skin the culture-induced inflammatory response.