Abstract
Objective
To quantitatively and qualitatively analyze the proteomic profile of teeth with acute apical abscesses (AAA) compared with teeth with chronic apical periodontitis (CAP) and to correlate the expression of detected human proteins with their main biological functions.
Materials and methods
Samples were obtained from root canals of 9 patients diagnosed with AAA and 9 with CAP. Samples were analyzed by reversed-phase liquid chromatography coupled to mass spectrometry. Label-free quantitative proteomic analysis was performed by Protein Lynx Global Service software. Differences in protein expression were calculated using the t-test (p < 0.05).
Results
In total, 246 human proteins were identified from all samples. Proteins exclusively found in the AAA group were mainly associated with the immunoinflammatory response and oxidative stress response. In the quantitative analysis, 17 proteins were upregulated (p < 0.05) in the AAA group, including alpha-1-acid glycoprotein, hemopexin, fibrinogen gamma chain, and immunoglobulin. Additionally, 61 proteins were downregulated (p < 0.05), comprising cathepsin G, moesin, gelsolin, and transketolase. Most of the proteins were from the extracellular matrix, cytoplasm, and nucleus.
Conclusions
The common proteins between the groups were mainly associated with the immune response at both expression levels. Upregulated proteins mostly belonged to the acute-phase proteins, while the downregulated proteins were associated with DNA/RNA regulation and repair, and structural function.
Clinical relevance
The host response is directly related to the development of apical abscesses. Thus, understanding the behavior of human proteins against the endodontic pathogens involved in this condition might contribute to the study of new approaches related to the treatment of this disease.
Similar content being viewed by others
References
Jacinto RC, Gomes BP, Ferraz CC, Zaia AA, Filho FJ (2003) Microbiological analysis of infected root canals from symptomatic and asymptomatic teeth with periapical periodontitis and the antimicrobial susceptibility of some isolated anaerobic bacteria. Oral Microbiol Immunol 18:285–292. https://doi.org/10.1034/j.1399-302x.2003.00078.x
Ricucci D, Siqueira JF Jr (2010) Biofilms and apical periodontitis: study of prevalence and association with clinical and histopathologic findings. J Endod 36:1277–1288. https://doi.org/10.1016/j.joen.2010.04.007
Siqueira JF Jr, Rocas IN (2013) Microbiology and treatment of acute apical abscesses. Clin Microbiol Rev 26:255–273. https://doi.org/10.1128/CMR.00082-12
George N, Flamiatos E, Kawasaki K, Kim N, Carriere C, Phan B, Joseph R, Strauss S, Kohli R, Choi D, Baumgartner JC, Sedgley C, Maier T, Machida CA (2016) Oral microbiota species in acute apical endodontic abscesses. J Oral Microbiol 8:30989. https://doi.org/10.3402/jom.v8.30989
Montagner F, Jacinto RC, Signoretti FG, Sanches PF, Gomes BP (2012) Clustering behavior in microbial communities from acute endodontic infections. J Endod 38:158–162. https://doi.org/10.1016/j.joen.2011.09.029
Siqueira JF Jr, Rocas IN, Souto R, Uzeda M, Colombo AP (2001) Microbiological evaluation of acute periradicular abscesses by DNA-DNA hybridization. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:451–457. https://doi.org/10.1067/moe.2001.118620
Umeda M, Minamikawa T, Komatsubara H, Shibuya Y, Yokoo S, Komori T (2003) Necrotizing fasciitis caused by dental infection: a retrospective analysis of 9 cases and a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:283–290. https://doi.org/10.1067/moe.2003.85
Azenha MR, Homsi G, Garcia IR Jr (2012) Multiple brain abscess from dental origin: case report and literature review. Oral Maxillofac Surg 16:393–397. https://doi.org/10.1007/s10006-011-0308-3
Cope AL, Francis N, Wood F, Chestnutt IG (2018) Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults. Cochrane Database Syst Rev 9:CD010136. https://doi.org/10.1002/14651858.CD010136.pub3
Wilkins MR, Sanchez JC, Gooley AA, Appel RD, Humphery-Smith I, Hochstrasser DF, Williams KL (1996) Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it. Biotechnol Genet Eng Rev 13:19–50. https://doi.org/10.1080/02648725.1996.10647923
Alfenas CF, Mendes TAO, Ramos HJO, Bruckner FP, Antunes HS, Rocas IN, Siqueira JF Jr, Provenzano JC (2017) Human exoproteome in acute apical abscesses. J Endod 43:1479–1485. https://doi.org/10.1016/j.joen.2017.04.019
Loureiro C, Buzalaf MAR, Pessan JP, Moraes FRN, Pela VT, Ventura TMO, Jacinto RC (2020) Comparative analysis of the proteomic profile of the dental pulp in different conditions. A pilot study Braz Dent J 31:319–336. https://doi.org/10.1590/0103-6440202003167
Silva PAO, Lima SMF, Freire MS, Murad AM, Franco OL, Rezende TMB (2021) Proteomic analysis of human dental pulp in different clinical diagnosis. Clin Oral Investig 25:3285–3295. https://doi.org/10.1007/s00784-020-03660-3
Provenzano JC, Siqueira JF Jr, Rocas IN, Domingues RR, Paes Leme AF, Silva MR (2013) Metaproteome analysis of endodontic infections in association with different clinical conditions. PLoS ONE 8:e76108. https://doi.org/10.1371/journal.pone.0076108
Loureiro C, Buzalaf MAR, Moraes FRN, Ventura TMO, Pela VT, Pessan JP, Jacinto RC (2021) Quantitative proteomic analysis in symptomatic and asymptomatic apical periodontitis. Int Endod J 54:834–847. https://doi.org/10.1111/iej.13480
Provenzano JC, Antunes HS, Alves FR, Rocas IN, Alves WS, Silva MR, Siqueira JF Jr (2016) Host-bacterial interactions in post-treatment apical periodontitis: a metaproteome analysis. J Endod 42:880–885. https://doi.org/10.1016/j.joen.2016.02.013
Francisco PA, Delboni MG, Lima AR, Xiao Y, Siqueira WL, Gomes B (2019) Proteomic profile of root canal contents in teeth with post-treatment endodontic disease. Int Endod J 52:451–460. https://doi.org/10.1111/iej.13021
Jacinto RC, Montagner F, Signoretti FG, Almeida GC, Gomes BP (2008) Frequency, microbial interactions, and antimicrobial susceptibility of Fusobacterium nucleatum and Fusobacterium necrophorum isolated from primary endodontic infections. J Endod 34:1451–1456. https://doi.org/10.1016/j.joen.2008.08.036
Ventura T, Ribeiro NR, Dionizio AS, Sabino IT, Buzalaf MAR (2018) Standardization of a protocol for shotgun proteomic analysis of saliva. J Appl Oral Sci 26:e20170561. https://doi.org/10.1590/1678-7757-2017-0561
Hsiao WW, Li KL, Liu Z, Jones C, Fraser-Liggett CM, Fouad AF (2012) Microbial transformation from normal oral microbiota to acute endodontic infections. BMC Genomics 13:345. https://doi.org/10.1186/1471-2164-13-345
Germolec DR, Shipkowski KA, Frawley RP, Evans E (2018) Markers of inflammation. Methods Mol Biol 1803:57–79. https://doi.org/10.1007/978-1-4939-8549-4_5
Moshage H (1997) Cytokines and the hepatic acute phase response. J Pathol 181:257–266. https://doi.org/10.1002/(SICI)1096-9896(199703)181:3%3c257::AID-PATH756%3e3.0.CO;2-U
Ceciliani F, Lecchi C (2019) The immune functions of alpha1 acid glycoprotein. Curr Protein Pept Sci 20:505–524. https://doi.org/10.2174/1389203720666190405101138
Gabay C, Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340:448–454. https://doi.org/10.1056/NEJM199902113400607
Watanabe T, Tanaka H, Nakao N, Mikami T, Suzuki M, Matsumoto T (1997) Anti Candida activity of induced transferrin in mice immunized with inactivated Candida albicans. Biol Pharm Bull 20:637–640. https://doi.org/10.1248/bpb.20.637
Bruhn KW, Spellberg B (2015) Transferrin-mediated iron sequestration as a novel therapy for bacterial and fungal infections. Curr Opin Microbiol 27:57–61. https://doi.org/10.1016/j.mib.2015.07.005
Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW (2014) Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development. Front Physiol 5:415. https://doi.org/10.3389/fphys.2014.00415
Korkmaz B, Horwitz MS, Jenne DE, Gauthier F (2010) Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol Rev 62:726–759. https://doi.org/10.1124/pr.110.002733
Xu K, Yen T, Geczy CL (2001) Il-10 up-regulates macrophage expression of the S100 protein S100A8. J Immunol 166:6358–6366. https://doi.org/10.4049/jimmunol.166.10.6358
Newton RA, Hogg N (1998) The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1 on neutrophils. J Immunol 160:1427–1435
Mosesson MW (2005) Fibrinogen and fibrin structure and functions. J Thromb Haemost 3:1894–1904. https://doi.org/10.1111/j.1538-7836.2005.01365.x
Farrell DH (2004) Pathophysiologic roles of the fibrinogen gamma chain. Curr Opin Hematol 11:151–155. https://doi.org/10.1097/01.moh.0000131440.02397.a4
Vengerfeldt V, Mandar R, Saag M, Piir A, Kullisaar T (2017) Oxidative stress in patients with endodontic pathologies. J Pain Res 10:2031–2040. https://doi.org/10.2147/JPR.S141366
Hernandez-Rios P, Pussinen PJ, Vernal R, Hernandez M (2017) Oxidative stress in the local and systemic events of apical periodontitis. Front Physiol 8:869. https://doi.org/10.3389/fphys.2017.00869
Ikwegbue PC, Masamba P, Oyinloye BE, Kappo AP (2017) Roles of heat shock proteins in apoptosis, oxidative stress, human inflammatory diseases, and cancer. Pharmaceuticals (Basel) 11https://doi.org/10.3390/ph11010002
Kalmar B, Greensmith L (2009) Induction of heat shock proteins for protection against oxidative stress. Adv Drug Deliv Rev 61:310–318. https://doi.org/10.1016/j.addr.2009.02.003
Feng H, Li Z, Du J, Sun J, Feng W, Li D, Liu S, Wang W, Liu H, Amizuka N, Li M (2018) Dual function of peroxiredoxin I in lipopolysaccharide-induced osteoblast apoptosis via reactive oxygen species and the apoptosis signal-regulating kinase 1 signaling pathway. Cell Death Discov 4:47. https://doi.org/10.1038/s41420-018-0050-9
Hussein H, Kishen A (2022) Application of proteomics in apical periodontitis. Frontiers in Dental Medicine 3:814603. https://doi.org/10.3389/fdmed.2022.814603
Acknowledgements
We are thankful to the Laboratory of Biochemistry from Bauru School of Dentistry, University of São Paulo, for technical assistance.
Funding
This work was supported by São Paulo State Research Foundation (FAPESP) (Grant numbers 2018/18741–0, 2019/14995–0) and the Coordination for the Improvement of Higher Education Personnel (CAPES)—Finance Code 001.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception, methodology, validation, and writing. Data acquisition was performed by Caroline Loureiro, Gladiston William Lobo Rodrigues, Júlia Guerra Andrade, and Rogério de Castilho Jacinto. Formal analysis was carried out by Caroline Loureiro, Talita Mendes Oliveira Ventura, and Vinícius Taioqui Pelá. Caroline Loureiro and Rogério de Castilho Jacinto acquired financing. Project administration and supervision were performed by Marília Afonso Rabelo Buzalaf, Juliano Pelim Pessan, and Rogério de Castilho Jacinto. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final article.
Corresponding author
Ethics declarations
Ethics approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki Declaration. and its later amendments or comparable ethical standards. This research was approved by the Research Ethics Committee of School of Dentistry, Araçatuba—UNESP (Nº 54191721.3.0000.5420).
Informed consent
Informed consent was obtained from all individual participants included in the study.
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Loureiro, C., Buzalaf, M.A.R., Ventura, T.M.O. et al. Teeth with acute apical abscess vs. teeth with chronic apical periodontitis: a quantitative and qualitative proteomic analysis. Clin Oral Invest 27, 591–601 (2023). https://doi.org/10.1007/s00784-022-04754-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00784-022-04754-w