Calcitonin gene‑related peptide induces IL‑6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893

Deng,Tian; Yang,Lan; Zheng,Zhichao; Li,Yuanjing; Ren,Wen; Wu,Caijuan; Guo,Lvhua

doi:10.3892/mmr.2017.7779

Calcitonin gene‑related peptide induces IL‑6 expression in RAW264.7 macrophages mediated by mmu_circRNA_007893

Authors:
- Tian Deng
- Lan Yang
- Zhichao Zheng
- Yuanjing Li
- Wen Ren
- Caijuan Wu
- Lvhua Guo
View Affiliations

Affiliations: Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510140, P.R. China
Published online on: October 12, 2017 https://doi.org/10.3892/mmr.2017.7779
Pages: 9367-9374
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Several circular RNAs (circRNAs) may have role important roles in biological processes, however, there is limited knowledge of circRNAs and their potential functions in RAW264.7 macrophages. The present study aimed to examine the expression of circRNAs and explore their effects on interleukin‑6 (IL‑6) expression induced by calcitonin gene‑related peptide (CGRP) in RAW264.7 macrophages. To identify circRNAs, the circRNA expression was measured in macrophages with or without CGRP stimulation. The interaction between circRNAs and microRNAs (miRs) were then identified using bioinformatic software and networks. In the current study, it was demonstrated that CGRP increased the expression of IL‑6 mRNA in a dose‑ and time‑dependent manner. Furthermore, mmu_circRNA_007893 was significantly increased in the CGRP‑stimulated macrophages. Silencing of mmu_circRNA_007893, IL‑6 mRNA expression was significantly decreased, whereas mmu‑miR‑485‑5p expression was markedly increased. Furthermore, when overexpression of mmu‑miR‑485‑5p, IL‑6 mRNA was markedly decreased. The results demonstrated that CGRP‑induced IL‑6 mRNA expression was mediated by mmu_circRNA_007893, and mmu_circRNA_007893 functioned as an endogenous mmu‑miR‑485‑5p sponge as part of induction of IL‑6 mRNA expression.

View Figures

View References

1	Amara SG, Jonas V, Rosenfeld MG, Ong ES and Evans RM: Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature. 298:240–244. 1982. View Article : Google Scholar : PubMed/NCBI
2	Li Q and Peng J: Sensory nerves and pancreatitis. Gland Surg. 3:284–292. 2014.PubMed/NCBI
3	Russell FA, King R, Smillie SJ, Kodji X and Brain SD: Calcitonin gene-related peptide: Physiology and pathophysiology. Physiol Rev. 94:1099–1142. 2014. View Article : Google Scholar : PubMed/NCBI
4	Fernandes ES, Schmidhuber SM and Brain SD: Sensory-nerve-derived neuropeptides: Possible therapeutic targets. Handb Exp Pharmacol. 1–416. 2009.
5	Gasperisic R, Kovacic U, Cör A and Skaleric U: Unilateral ligature-induced periodontitis influences the expression of neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats. Arch Oral Bio. 53:659–665. 2008. View Article : Google Scholar
6	Baliu-Piqué M, Jusek G and Holzmann B: Neuroimmunological communication via CGRP promotes the development of a regulatory phenotype in TLR4-stimulated macrophages. Eur J Immunol. 44:3708–3716. 2014. View Article : Google Scholar : PubMed/NCBI
7	Fernandez S, Knopf MA, Bjork SK and McGillis JP: Bone marrow-derived macrophages express functional CGRP receptors and respond to CGRP by increasing transcription of c-fos and IL-6 mRNA. Cell Immunol. 209:140–148. 2001. View Article : Google Scholar : PubMed/NCBI
8	Yang W, Xv M, Yang WC, Wang N, Zhang XZ and Li WZ: Exogenous α-calcitonin gene-related peptide attenuates lipopolysaccharide-induced acute lung injury in rats. Mol Med Rep. 12:2181–2188. 2015. View Article : Google Scholar : PubMed/NCBI
9	Liu J, Chen M and Wang X: Calcitonin gene-related peptide inhibits lipopolysaccharide-induced interleukin-12 release from mouse peritoneal macrophages, mediated by the cAMP pathway. Immunology. 101:61–67. 2000. View Article : Google Scholar : PubMed/NCBI
10	Kurashige C, Hosono K, Matsuda H, Tsujikawa K, Okamoto H and Majima M: Roles of receptor activity-modifying protein 1 in angiogenesis and lymphangiogenesis during skin wound healing in mice. FASEB J. 28:1237–1247. 2014. View Article : Google Scholar : PubMed/NCBI
11	Ma W, Dumont Y, Vercauteren F and Quirion R: Lipopolysaccharide induces calcitonin gene-related peptide in the RAW264.7 macrophage cell line. Immunology. 130:399–409. 2010. View Article : Google Scholar : PubMed/NCBI
12	Holzmann B: Antiinflammatory activities of CGRP modulating innate immune responses in health and disease. Curr Protein Pept Sci. 14:268–274. 2013. View Article : Google Scholar : PubMed/NCBI
13	Cocquerelle C, Mascrez B, Hétuin D and Bailleul B: Mis-splicing yields circular RNA molecules. FASEB J. 7:155–160. 1993.PubMed/NCBI
14	Surono A, Takeshima Y, Wibawa T, Ikezawa M, Nonaka I and Matsuo M: Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing. Hum Mol Genet. 8:493–500. 1999. View Article : Google Scholar : PubMed/NCBI
15	Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF and Sharpless NE: Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19:141–157. 2013. View Article : Google Scholar : PubMed/NCBI
16	Meczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, et al: Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 495:333–338. 2013. View Article : Google Scholar : PubMed/NCBI
17	Salzman J, Gawad C, Wang PL, Lacayo N and Brown PO: Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One. 7:e307332012. View Article : Google Scholar : PubMed/NCBI
18	Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L and Chen LL: Circular intronic long noncoding RNAs. Mol Cell. 51:792–806. 2013. View Article : Google Scholar : PubMed/NCBI
19	Ebbesen KK, Kjems J and Hansen TB: Circular RNAs: Identification, biogenesis and function. Biochim Biophys Acta. 1859:163–168. 2016. View Article : Google Scholar : PubMed/NCBI
20	Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK and Kjems J: Natural RNA circles function as efficient microRNA sponges. Nature. 495:384–388. 2013. View Article : Google Scholar : PubMed/NCBI
21	Thomas LF and Saetrom P: Circular RNAs are depleted of polymorphisms at microRNA binding site. Bioinformatics. 30:2243–2246. 2014. View Article : Google Scholar : PubMed/NCBI
22	Westholm JO, Miura P, Olson S, Shenker S, Joseph B, Sanfilippo P, Celniker SE, Graveley BR and Lai EC: Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Rep. 9:1966–1980. 2014. View Article : Google Scholar : PubMed/NCBI
23	Liu Q, Zhang X, Hu X, Dai L, Fu X, Zhang J and Ao Y: Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 ‘Sponge’ in human cartilage degradation. Sci Rep. 6:225722016. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Lin SP, Ye S, Long Y, Fan Y, Mao HF, Chen MT and Ma QJ: Circular RNA expression alterations are involved in OGD/R-induced neuron injury. Biochem Biophys Res Commun. 471:52–56. 2016. View Article : Google Scholar : PubMed/NCBI
26	Dou C, Cao Z, Yang B, Ding N, Hou T, Luo F, Kang F, Li J, Yang X, Jiang H, et al: Changing expression profiles of lncRNAs, mRNAs, circRNAs and miRNAs during osteoclastogenesis. Sci Rep. 6:214992016. View Article : Google Scholar : PubMed/NCBI
27	Qu S, Song W, Yang X, Wang J, Zhang R, Zhang Z, Zhang H and Li H: Microarray expression profile of circular RNAs in human pancreatic ductal adenocarcinoma. Genom Data. 5:385–387. 2015. View Article : Google Scholar : PubMed/NCBI
28	Wang YH, Yu XH, Luo SS and Han H: Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell aging. Immun Aging. 12:172015. View Article : Google Scholar
29	Jing LL and Mo XM: Reduced miR-485-5p expression predicts poor prognosis in patients with gastric cancer. Eur Rev Med Pharmacol Sci. 20:1516–1520. 2016.PubMed/NCBI
30	Kang M, Ren MP, Zhao L, Li CP and Deng MM: miR-485-5p acts as a negative regulator in gastric cancer progression by targeting flotillin-1. Am J Transl Res. 7:2212–2222. 2015.PubMed/NCBI
31	Correia NC, Melão A, Póvoa V, Sarmento L, Gómez de Cedrón M, Malumbres M, Enguita FJ and Barata JT: microRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia. Oncotarget. 7:8268–8281. 2016. View Article : Google Scholar : PubMed/NCBI