Skip to main content
Top
Published in: Clinical Oral Investigations 10/2020

01-10-2020 | Root Canal Debridement | Original Article

Clinical endodontic procedures modulate periapical cytokine and chemokine gene expressions

Authors: Lucas Moreira Maia, Marcela Carvalho Espaladori, Julia Maria Braga Diniz, Warley Luciano Faria Tavares, Luciana Carla Neves de Brito, Leda Quércia Vieira, Antônio Paulino Ribeiro Sobrinho

Published in: Clinical Oral Investigations | Issue 10/2020

Login to get access

Abstract

Objectives

To identify the gene expression of the cytokines IL-9, TNF-α, IL-1, INF-γ, IL-17A, and IL-10 and the chemokines CCL-2/MCP-1 and CCR-6 in the periapical fluid of human root canal infections.

Materials and methods

Twenty samples were collected immediately and 7 days after the cleaning and shaping procedures (after reducing the intracanal microbial load) in an attempt to characterize the expression of these genes. The endogenous expression levels of cytokines and chemokines were analyzed by real-time polymerase chain reaction. The Shapiro-Wilk and the Wilcoxon tests analyzed data.

Results

Significantly higher levels of the IL-9, INF-γ, TNF-α, IL-1, and IL-10 markers on day 7 were observed compared with day 0 (p < 0.05). However, IL-17A and the chemokines CCL-2/MCP-1 and CCR-6 did not show a significant difference in mRNA expression when comparing both timepoints (p > 0.05).

Conclusions

The clinical variation of the periapical immune status after endodontic therapy suggests that the cytokine and chemokine-mediated pro-inflammatory response appears to be modulated in an IL-10/IL-9-dependent manner.

Clinical relevance

Few studies have investigated the role of Th9 cells in periapical lesions. IL-9 presents exciting plasticity, performing immunosuppressive actions, and it is also capable of changing their phenotype in the presence of IL-17. Hence, it is relevant to investigate its role in the context of the known mediators involved the periapical immune process.
Literature
1.
go back to reference Stashenko P, Yu SM, Wang CY (1992) Kinetics of immune cell and bone resorptive responses to endodontic infections. J Endod 18:422–426CrossRef Stashenko P, Yu SM, Wang CY (1992) Kinetics of immune cell and bone resorptive responses to endodontic infections. J Endod 18:422–426CrossRef
2.
go back to reference Jontell M, Okiji T, Dahlgren U, Bergenholtz G (1998) Immune defense mechanisms of the dental pulp. Crit Rev Oral Biol Med 9:179–200CrossRef Jontell M, Okiji T, Dahlgren U, Bergenholtz G (1998) Immune defense mechanisms of the dental pulp. Crit Rev Oral Biol Med 9:179–200CrossRef
3.
go back to reference Sundqvist G (1992) Associations between microbial species in dental root canal infections. Oral Microbiol Immunol 7:257–262CrossRef Sundqvist G (1992) Associations between microbial species in dental root canal infections. Oral Microbiol Immunol 7:257–262CrossRef
4.
go back to reference Marton IJ, Kiss C (2014) Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 40:155–163CrossRef Marton IJ, Kiss C (2014) Overlapping protective and destructive regulatory pathways in apical periodontitis. J Endod 40:155–163CrossRef
5.
go back to reference Marton IJ, Kiss C (2000) Protective and destructive immune reactions in apical periodontitis. Oral Microbiol Immunol 15:139–150CrossRef Marton IJ, Kiss C (2000) Protective and destructive immune reactions in apical periodontitis. Oral Microbiol Immunol 15:139–150CrossRef
6.
go back to reference Fukada SY, Silva TA, Garlet GP, Rosa AL, da Silva JS, Cunha FQ (2009) Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases. Oral Microbiol Immunol 24:25–31CrossRef Fukada SY, Silva TA, Garlet GP, Rosa AL, da Silva JS, Cunha FQ (2009) Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases. Oral Microbiol Immunol 24:25–31CrossRef
7.
go back to reference de Brito LCN, Teles FR, Teles RP, Totola AH, Vieira LQ, Ribeiro Sobrinho AP (2012) T-lymphocyte and cytokine expression in human inflammatory periapical lesions. J Endod 38:481–485CrossRef de Brito LCN, Teles FR, Teles RP, Totola AH, Vieira LQ, Ribeiro Sobrinho AP (2012) T-lymphocyte and cytokine expression in human inflammatory periapical lesions. J Endod 38:481–485CrossRef
8.
go back to reference Silva TA, Garlet GP, Lara VS, Martins W Jr, Silva JS, Cunha FQ (2005) Differential expression of chemokines and chemokine receptors in inflammatory periapical diseases. Oral Microbiol Immunol 20:310–316CrossRef Silva TA, Garlet GP, Lara VS, Martins W Jr, Silva JS, Cunha FQ (2005) Differential expression of chemokines and chemokine receptors in inflammatory periapical diseases. Oral Microbiol Immunol 20:310–316CrossRef
9.
go back to reference Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242CrossRef Rossi D, Zlotnik A (2000) The biology of chemokines and their receptors. Annu Rev Immunol 18:217–242CrossRef
10.
go back to reference Aranha AM, Repeke CE, Garlet TP et al (2013) Evidence supporting a protective role for Th9 and Th22 cytokines in human and experimental periapical lesions. J Endod 39:83–87CrossRef Aranha AM, Repeke CE, Garlet TP et al (2013) Evidence supporting a protective role for Th9 and Th22 cytokines in human and experimental periapical lesions. J Endod 39:83–87CrossRef
11.
go back to reference Araujo-Pires AC, Francisconi CF, Biguetti CC, Cavalla F, Aranha AM, Letra A, Trombone AP, Faveri M, Silva RM, Garlet GP (2014) Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. J Appl Oral Sci 22:336–346CrossRef Araujo-Pires AC, Francisconi CF, Biguetti CC, Cavalla F, Aranha AM, Letra A, Trombone AP, Faveri M, Silva RM, Garlet GP (2014) Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status. J Appl Oral Sci 22:336–346CrossRef
12.
go back to reference Bambirra W Jr, Maciel KF, Thebit MM, de Brito LCN, Vieira LQ, Ribeiro Sobrinho AP (2015) Assessment of apical expression of alpha-2 integrin, heat shock protein, and proinflammatory and immunoregulatory cytokines in response to endodontic infection. J Endod 41:1085–1090CrossRef Bambirra W Jr, Maciel KF, Thebit MM, de Brito LCN, Vieira LQ, Ribeiro Sobrinho AP (2015) Assessment of apical expression of alpha-2 integrin, heat shock protein, and proinflammatory and immunoregulatory cytokines in response to endodontic infection. J Endod 41:1085–1090CrossRef
13.
go back to reference de Brito LCN, Teles FR, Teles RP, Nogueira PM, Vieira LQ, Ribeiro Sobrinho AP (2015) Immunological profile of periapical endodontic infections from HIV- and HIV+ patients. Int Endod J 48:533–541CrossRef de Brito LCN, Teles FR, Teles RP, Nogueira PM, Vieira LQ, Ribeiro Sobrinho AP (2015) Immunological profile of periapical endodontic infections from HIV- and HIV+ patients. Int Endod J 48:533–541CrossRef
14.
go back to reference Henriques LC, de Brito LCN, Tavares WL, Vieira LQ, Ribeiro Sobrinho AP (2011) Cytokine analysis in lesions refractory to endodontic treatment. J Endod 37:1659–1662CrossRef Henriques LC, de Brito LCN, Tavares WL, Vieira LQ, Ribeiro Sobrinho AP (2011) Cytokine analysis in lesions refractory to endodontic treatment. J Endod 37:1659–1662CrossRef
15.
go back to reference Ferreira SB, de Brito LCN, Oliveira MP et al (2015) Periapical cytokine expression in sickle cell disease. J Endod 41:358–362CrossRef Ferreira SB, de Brito LCN, Oliveira MP et al (2015) Periapical cytokine expression in sickle cell disease. J Endod 41:358–362CrossRef
16.
go back to reference Kawashima N, Stashenko P (1999) Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch Oral Biol 44:55–66CrossRef Kawashima N, Stashenko P (1999) Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation. Arch Oral Biol 44:55–66CrossRef
17.
go back to reference Jager A, Kuchroo VK (2010) Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol 72:173–184CrossRef Jager A, Kuchroo VK (2010) Effector and regulatory T-cell subsets in autoimmunity and tissue inflammation. Scand J Immunol 72:173–184CrossRef
18.
go back to reference Mucida D, Cheroutre H (2010) The many face-lifts of CD4 T helper cells. Adv Immunol 107:139–152CrossRef Mucida D, Cheroutre H (2010) The many face-lifts of CD4 T helper cells. Adv Immunol 107:139–152CrossRef
19.
go back to reference Li H, Rostami A (2010) IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity. J NeuroImmune Pharmacol 5:198–209CrossRef Li H, Rostami A (2010) IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity. J NeuroImmune Pharmacol 5:198–209CrossRef
20.
go back to reference Nowak EC, Weaver CT, Turner H, Begum-Haque S, Becher B, Schreiner B, Coyle AJ, Kasper LH, Noelle RJ (2009) IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med 206:1653–1660CrossRef Nowak EC, Weaver CT, Turner H, Begum-Haque S, Becher B, Schreiner B, Coyle AJ, Kasper LH, Noelle RJ (2009) IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med 206:1653–1660CrossRef
21.
go back to reference Tan C, Aziz MK, Lovaas JD et al (2010) Antigen-specific Th9 cells exhibit uniqueness in their kinetics of cytokine production and short retention at the inflammatory site. J Immunol 185:6795–6801CrossRef Tan C, Aziz MK, Lovaas JD et al (2010) Antigen-specific Th9 cells exhibit uniqueness in their kinetics of cytokine production and short retention at the inflammatory site. J Immunol 185:6795–6801CrossRef
22.
go back to reference Moller AJ (1966) Microbiological examination of root canals and periapical tissues of human teeth. Methodological studies. Odontol Tidskr 74:1–380 Moller AJ (1966) Microbiological examination of root canals and periapical tissues of human teeth. Methodological studies. Odontol Tidskr 74:1–380
23.
go back to reference Rodrigues RCV, Zandi H, Kristoffersen AK et al (2017) Influence of the apical preparation size and the irrigant type on bacterial reduction in root canal-treated teeth with apical periodontitis. J Endod 43:1058–1063CrossRef Rodrigues RCV, Zandi H, Kristoffersen AK et al (2017) Influence of the apical preparation size and the irrigant type on bacterial reduction in root canal-treated teeth with apical periodontitis. J Endod 43:1058–1063CrossRef
24.
go back to reference Barbosa Silva MJ, Vieira LQ, Ribeiro Sobrinho AP (2008) The effects of mineral trioxide aggregates on cytokine production by mouse pulp tissue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:e70–e76CrossRef Barbosa Silva MJ, Vieira LQ, Ribeiro Sobrinho AP (2008) The effects of mineral trioxide aggregates on cytokine production by mouse pulp tissue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:e70–e76CrossRef
25.
go back to reference Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108CrossRef Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108CrossRef
26.
go back to reference Cotti E, Schirru E, Acquas E, Usai P (2014) An overview on biologic medications and their possible role in apical periodontitis. J Endod 40:1902–1911CrossRef Cotti E, Schirru E, Acquas E, Usai P (2014) An overview on biologic medications and their possible role in apical periodontitis. J Endod 40:1902–1911CrossRef
27.
go back to reference Stessman HA, Bernier R, Eichler EE (2014) A genotype-first approach to defining the subtypes of a complex disease. Cell 156:872–877CrossRef Stessman HA, Bernier R, Eichler EE (2014) A genotype-first approach to defining the subtypes of a complex disease. Cell 156:872–877CrossRef
29.
go back to reference Takeichi O, Saito I, Tsurumachi T, Moro I, Saito T (1996) Expression of inflammatory cytokine genes in vivo by human alveolar bone-derived polymorphonuclear leukocytes isolated from chronically inflamed sites of bone resorption. Calcif Tissue Int 58:244–248PubMed Takeichi O, Saito I, Tsurumachi T, Moro I, Saito T (1996) Expression of inflammatory cytokine genes in vivo by human alveolar bone-derived polymorphonuclear leukocytes isolated from chronically inflamed sites of bone resorption. Calcif Tissue Int 58:244–248PubMed
30.
go back to reference Bazzoni F, Tamassia N, Rossato M, Cassatella MA (2010) Understanding the molecular mechanisms of the multifaceted IL-10-mediated anti-inflammatory response: lessons from neutrophils. Eur J Immunol 40:2360–2368CrossRef Bazzoni F, Tamassia N, Rossato M, Cassatella MA (2010) Understanding the molecular mechanisms of the multifaceted IL-10-mediated anti-inflammatory response: lessons from neutrophils. Eur J Immunol 40:2360–2368CrossRef
31.
go back to reference Ivanovski SJ, Farah CS (2007) Alveolar bone loss in T helper 1/T helper 2 cytokine-deficient mice. J Periodontal Res 42:97–103CrossRef Ivanovski SJ, Farah CS (2007) Alveolar bone loss in T helper 1/T helper 2 cytokine-deficient mice. J Periodontal Res 42:97–103CrossRef
32.
go back to reference Colic M, Gazivoda D, Vucevic D et al (2009) Regulatory T-cells in periapical lesions. J Dent Res 88:997–1002CrossRef Colic M, Gazivoda D, Vucevic D et al (2009) Regulatory T-cells in periapical lesions. J Dent Res 88:997–1002CrossRef
33.
go back to reference Xing J, Wu Y, Ni B (2011) Th9: a new player in asthma pathogenesis? J Asthma 48:115–125CrossRef Xing J, Wu Y, Ni B (2011) Th9: a new player in asthma pathogenesis? J Asthma 48:115–125CrossRef
34.
go back to reference Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SL (1996) Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol 157:4602–4608PubMed Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SL (1996) Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol 157:4602–4608PubMed
35.
go back to reference Lisignoli G, Manferdini C, Codeluppi K, Piacentini A, Grassi F, Cattini L, Filardo G, Facchini A (2009) CCL20/CCR6 chemokine/receptor expression in bone tissue from osteoarthritis and rheumatoid arthritis patients: different response of osteoblasts in the two groups. J Cell Physiol 221:154–160CrossRef Lisignoli G, Manferdini C, Codeluppi K, Piacentini A, Grassi F, Cattini L, Filardo G, Facchini A (2009) CCL20/CCR6 chemokine/receptor expression in bone tissue from osteoarthritis and rheumatoid arthritis patients: different response of osteoblasts in the two groups. J Cell Physiol 221:154–160CrossRef
36.
go back to reference Santos FR, Moyses RM, Montenegro FL, Jorgetti V, Noronha IL (2003) IL-1beta, TNF-alpha, TGF-beta, and bFGF expression in bone biopsies before and after parathyroidectomy. Kidney Int 63:899–907CrossRef Santos FR, Moyses RM, Montenegro FL, Jorgetti V, Noronha IL (2003) IL-1beta, TNF-alpha, TGF-beta, and bFGF expression in bone biopsies before and after parathyroidectomy. Kidney Int 63:899–907CrossRef
37.
go back to reference Velickovic M, Pejnovic N, Mitrovic S et al (2015) ST2 deletion increases inflammatory bone destruction in experimentally induced periapical lesions in mice. J Endod 41:369–375CrossRef Velickovic M, Pejnovic N, Mitrovic S et al (2015) ST2 deletion increases inflammatory bone destruction in experimentally induced periapical lesions in mice. J Endod 41:369–375CrossRef
Metadata
Title
Clinical endodontic procedures modulate periapical cytokine and chemokine gene expressions
Authors
Lucas Moreira Maia
Marcela Carvalho Espaladori
Julia Maria Braga Diniz
Warley Luciano Faria Tavares
Luciana Carla Neves de Brito
Leda Quércia Vieira
Antônio Paulino Ribeiro Sobrinho
Publication date
01-10-2020
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 10/2020
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-020-03247-y

Other articles of this Issue 10/2020

Clinical Oral Investigations 10/2020 Go to the issue