RvD1(n-3 DPA) Downregulates the Transcription of Pro-Inflammatory Genes in Oral Epithelial Cells and Reverses Nuclear Translocation of Transcription Factor p65 after TNF-α Stimulation.
Balta, Maria G.; Schreurs, Olav; Halder, Rashiet al.
2022 • In International Journal of Molecular Sciences, 23 (23)
[en] Specialized pro-resolving mediators (SPMs) are multifunctional lipid mediators that participate in the resolution of inflammation. We have recently described that oral epithelial cells (OECs) express receptors of the SPM resolvin RvD1(n-3 DPA) and that cultured OECs respond to RvD1(n-3 DPA) addition by intracellular calcium release, nuclear receptor translocation and transcription of genes coding for antimicrobial peptides. The aim of the present study was to assess the functional outcome of RvD1(n-3 DPA)-signaling in OECs under inflammatory conditions. To this end, we performed transcriptomic analyses of TNF-α-stimulated cells that were subsequently treated with RvD1(n-3 DPA) and found significant downregulation of pro-inflammatory nuclear factor kappa B (NF-κB) target genes. Further bioinformatics analyses showed that RvD1(n-3 DPA) inhibited the expression of several genes involved in the NF-κB activation pathway. Confocal microscopy revealed that addition of RvD1(n-3 DPA) to OECs reversed TNF-α-induced nuclear translocation of NF-κB p65. Co-treatment of the cells with the exportin 1 inhibitor leptomycin B indicated that RvD1(n-3 DPA) increases nuclear export of p65. Taken together, our observations suggest that SPMs also have the potential to be used as a therapeutic aid when inflammation is established.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Disciplines :
Human health sciences: Multidisciplinary, general & others Life sciences: Multidisciplinary, general & others
Author, co-author :
Balta, Maria G.
Schreurs, Olav
Halder, Rashi ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Scientific Central Services
Küntziger, Thomas M.
Saetre, Frank
Blix, Inger Johanne S.
Baekkevold, Espen S.
Glaab, Enrico ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Biomedical Data Science
Schenck, Karl
External co-authors :
yes
Language :
English
Title :
RvD1(n-3 DPA) Downregulates the Transcription of Pro-Inflammatory Genes in Oral Epithelial Cells and Reverses Nuclear Translocation of Transcription Factor p65 after TNF-α Stimulation.
Publication date :
2022
Journal title :
International Journal of Molecular Sciences
ISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Diamond G. Beckloff N. Ryan L.K. Host defense peptides in the oral cavity and the lung: Similarities and differences J. Dent. Res. 2008 87 915 927 10.1177/154405910808701011 18809744
Barnig C. Bezema T. Calder P.C. Charloux A. Frossard N. Garssen J. Haworth O. Dilevskaya K. Levi-Schaffer F. Lonsdorfer E. et al. Activation of Resolution Pathways to Prevent and Fight Chronic Inflammation: Lessons From Asthma and Inflammatory Bowel Disease Front. Immunol. 2019 10 1699 10.3389/fimmu.2019.01699 31396220
Cn S. Novel lipid mediators and resolution mechanisms in acute inflammation: To resolve or not? Am. J. Pathol. 2010 177 1576 1591
Balta M.G. Loos B.G. Nicu E.A. Emerging Concepts in the Resolution of Periodontal Inflammation: A Role for Resolvin E1 Front. Immunol. 2017 8 1682 10.3389/fimmu.2017.01682 29312286
Croasdell A. Sime P.J. Phipps R.P. Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes Faseb J. 2016 30 3181 3193 10.1096/fj.201600375R 27256622
El Kholy K. Freire M. Chen T. Van Dyke T.E. Resolvin E1 Promotes Bone Preservation under Inflammatory Conditions Front. Immunol. 2018 9 1300 10.3389/fimmu.2018.01300 29946319
Tang Y. Zhang M.J. Hellmann J. Kosuri M. Bhatnagar A. Spite M. Proresolution therapy for the treatment of delayed healing of diabetic wounds Diabetes 2013 62 618 627 10.2337/db12-0684
Bohr S. Patel S.J. Sarin D. Irimia D. Yarmush M.L. Berthiaume F. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model Wound Repair Regen. 2013 21 35 43 10.1111/j.1524-475X.2012.00853.x
Papathanasiou E. Trotman C.A. Scott A.R. Van Dyke T.E. Current and Emerging Treatments for Postsurgical Cleft Lip Scarring: Effectiveness and Mechanisms J. Dent. Res. 2017 96 1370 1377 10.1177/0022034517717261 28650705
Balta M.G. Papathanasiou E. Blix I.J. Van Dyke T.E. Host Modulation and Treatment of Periodontal Disease J. Dent. Res. 2021 100 798 809 10.1177/0022034521995157
Hellmann J. Sansbury B.E. Wong B. Li X. Singh M. Nuutila K. Chiang N. Eriksson E. Serhan C.N. Spite M. Biosynthesis of D-Series Resolvins in Skin Provides Insights into their Role in Tissue Repair J. Investig. Derm. 2018 138 2051 2060 10.1016/j.jid.2018.03.1498 29559341
Saito P. Melo C.P.B. Martinez R.M. Fattori V. Cezar T.L.C. Pinto I.C. Bussmann A.J.C. Vignoli J.A. Georgetti S.R. Baracat M.M. et al. The Lipid Mediator Resolvin D1 Reduces the Skin Inflammation and Oxidative Stress Induced by UV Irradiation in Hairless Mice Front. Pharmacol. 2018 9 1242 10.3389/fphar.2018.01242 30429790
Balta M.G. Schreurs O. Hansen T.V. Tungen J.E. Vik A. Glaab E. Küntziger T.M. Schenck K. Baekkevold E.S. Blix I.J.S. Expression and function of resolvin RvD1(n-3 DPA) receptors in oral epithelial cells Eur. J. Oral Sci. 2022 130 e12883 10.1111/eos.12883 35808844
Ishida T. Yoshida M. Arita M. Nishitani Y. Nishiumi S. Masuda A. Mizuno S. Takagawa T. Morita Y. Kutsumi H. et al. Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis Inflamm. Bowel Dis. 2010 16 87 95 10.1002/ibd.21029 19572372
Colby J.K. Abdulnour R.-E.E. Sham H.P. Dalli J. Colas R.A. Winkler J.W. Hellmann J. Wong B. Cui Y. El-Chemaly S. et al. Resolvin D3 and Aspirin-Triggered Resolvin D3 Are Protective for Injured Epithelia Am. J. Pathol. 2016 186 1801 1813 10.1016/j.ajpath.2016.03.011
Zhang J. Wang M. Ye J. Liu J. Xu Y. Wang Z. Ye D. Zhao M. Wan J. The Anti-inflammatory Mediator Resolvin E1 Protects Mice Against Lipopolysaccharide-Induced Heart Injury Front. Pharmacol. 2020 11 203 10.3389/fphar.2020.00203
Chindelevitch L. Ziemek D. Enayetallah A. Randhawa R. Sidders B. Brockel C. Huang E.S. Causal reasoning on biological networks: Interpreting transcriptional changes Bioinformatics 2012 28 1114 1121 10.1093/bioinformatics/bts090
Dalli J. Colas R.A. Serhan C.N. Novel n-3 Immunoresolvents: Structures and Actions Sci. Rep. 2013 3 1940 10.1038/srep01940
Tungen J.E. Gerstmann L. Vik A. De Matteis R. Colas R.A. Dalli J. Chiang N. Serhan C.N. Kalesse M. Hansen T.V. Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1(n-3 DPA) Chemistry 2019 25 1476 1480 10.1002/chem.201806029
Vik A. Dalli J. Hansen T.V. Recent advances in the chemistry and biology of anti-inflammatory and specialized pro-resolving mediators biosynthesized from n-3 docosapentaenoic acid Bioorganic Med. Chem. Lett. 2017 27 2259 2266 10.1016/j.bmcl.2017.03.079
Guo Y. Tu Y.H. Wu X. Ji S. Shen J.L. Wu H.M. Fei G.H. ResolvinD1 Protects the Airway Barrier Against Injury Induced by Influenza A Virus Through the Nrf2 Pathway Front. Cell. Infect. Microbiol. 2020 10 616475 10.3389/fcimb.2020.616475 33643931
Odusanwo O. Chinthamani S. McCall A. Duffey M.E. Baker O.J. Resolvin D1 prevents TNF-α-mediated disruption of salivary epithelial formation Am. J. Physiol. Cell. Physiol. 2012 302 C1331 C1345 10.1152/ajpcell.00207.2011
Mizraji G. Heyman O. Van Dyke T.E. Wilensky A. Resolvin D2 Restrains Th1 Immunity and Prevents Alveolar Bone Loss in Murine Periodontitis Front. Immunol. 2018 9 785 10.3389/fimmu.2018.00785
Li C. Wu X. Liu S. Shen D. Zhu J. Liu K. Role of Resolvins in the Inflammatory Resolution of Neurological Diseases Front. Pharmacol. 2020 11 612 10.3389/fphar.2020.00612
Lopategi A. Flores-Costa R. Rius B. López-Vicario C. Alcaraz-Quiles J. Titos E. Clària J. Frontline Science: Specialized proresolving lipid mediators inhibit the priming and activation of the macrophage NLRP3 inflammasome J. Leukoc. Biol. 2019 105 25 36 10.1002/JLB.3HI0517-206RR
Giridharan S. Srinivasan M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation J. Inflamm. Res. 2018 11 407 419 10.2147/JIR.S140188
Azmi A.S. Uddin M.H. Mohammad R.M. The nuclear export protein XPO1—From biology to targeted therapy Nat. Rev. Clin. Oncol. 2021 18 152 169 10.1038/s41571-020-00442-4 33173198
Schreurs O. Karatsaidis A. Balta M.G. Grung B. Hals E.K.B. Schenck K. Expression of keratins 8, 18, and 19 in epithelia of atrophic oral lichen planus Eur. J. Oral Sci. 2020 128 7 17 10.1111/eos.12666 31994252
de Sena Brandine G. Smith A.D. Falco: High-speed FastQC emulation for quality control of sequencing data F1000Res 2019 8 1874 10.12688/f1000research.21142.1
Liao Y. Smyth G.K. Shi W. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads Nucleic Acids Res. 2019 47 e47 10.1093/nar/gkz114
R Computer Team R: A Language and Environment for Statistical Computing Available online: https://www.R-project.org/ (accessed on 11 April 2022)
Robinson M.D. McCarthy D.J. Smyth G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data Bioinformatics 2010 26 139 140 10.1093/bioinformatics/btp616 19910308
Wu T. Hu E. Xu S. Chen M. Guo P. Dai Z. Feng T. Zhou L. Tang W. Zhan L. et al. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data Innovation 2021 2 100141 10.1016/j.xinn.2021.100141 34557778
Liberzon A. A description of the Molecular Signatures Database (MSigDB) Web site Methods Mol Biol 2014 1150 153 160
Benjamini Y. Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing J. R. Stat. Soc. Ser. B Methodol. 1995 57 289 300 10.1111/j.2517-6161.1995.tb02031.x
Szklarczyk D. Gable A.L. Nastou K.C. Lyon D. Kirsch R. Pyysalo S. Doncheva N.T. Legeay M. Fang T. Bork P. et al. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets Nucleic Acids Res 2021 49 D605 D612 10.1093/nar/gkaa1074
