[Frontiers in Bioscience E4, 1478-1495, January 1, 2012]

MicroRNAs and other mechanisms regulate interleukin-17 cytokines and receptors

Jietang Mai1, Anthony Virtue1, Erin Maley1, Tran Tran1, Ying Yin1, Shu Meng1, Meghana Pansuria1, Xiaohua Jiang1,

Hong Wang1, Xiao-Feng Yang1

1Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, U.S.A.

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Methods
3.1. Tissue expression profiles of genes encoding IL-17 cytokines, IL-17 receptors, RORC, and TRAF3IP2
3.2. Alternative spliced isoforms of IL-17 cytokines and IL-17 receptors
3.3. Presence of AU-rich elements and functional motifs in 3' untranslated regions of IL-17 cytokines and IL-17 receptors
3.4. Correlation of the ratios of tissue SAH versus SAM concentrations with the expression levels of IL-17 cytokine and receptor mRNA transcripts
3.5. MicroRNA Interaction with the mRNAs of IL-17 Cytokines and IL-17 Receptors
4. Results
4.1. Most of IL-17 cytokines are not constitutively expressed in the tissues examined, but several IL-17 receptors and TRAF3IP2 are ubiquitously expressed
4.2. Heart and vascular tissues are in the second tier of readiness to respond to IL-17 cytokine stimulation, which requires the upregulation of IL-17 receptor complex components
4.3. Alternative promoter and alternative splicing regulate the structures and expressions of IL-17 cytokines and receptors
4.4. Higher hypomethylation status is positively associated with higher expressions of IL-17 receptors and lower expression of IL-17d in mouse tissue
4.5. RNA binding proteins may regulate the mRNA stability and translation of IL-17 cytokines and receptors
4.6. MicroRNAs may regulate the mRNA stability and translation of IL-17 cytokines and receptors independently or via interaction with RNA binding protein-mediated mechanism
5. Discussion
6. Acknowledgements
7. References

1. ABSTRACT

Interleukin-17 cytokines are a family of pro-inflammatory cytokines. Our current studies found: i) IL-17 cytokines are not ubiquitously expressed, but several receptors and TRAF3IP2 are ubiquitously expressed in tissues with a few exceptions; ii) heart and vascular tissue are in the second tier of readiness to respond to IL-17 cytokine stimulation; iii) alternative transcription starting sites and alternative spliced isoforms are found in IL-17 cytokine and receptor transcripts; iv) higher hypomethylation status is associated with higher expressions of IL-17 receptors; v) the binding sites of several RNA binding proteins are found in the 3'UTRs of the mRNAs of IL-17 cytokines and receptors; and vi) numerous microRNA binding sites are statistically equivalent to that of experimentally verified microRNAs-mRNA interactions in the 3'UTRs of IL-17 cytokine and receptor mRNAs. These results suggest that mechanisms including alternative promoters, alternative splicing, RNA binding proteins, and microRNAs regulate the structures and expressions of IL-17 cytokines and receptors. These results provide an insight into the roles of IL-17 in mediating inflammation and immunity.