Abstract
Chemerin is a chemoattractant protein that directs inflammatory cells that express its receptor chemokine receptor-like 1 (ChemR23) towards sites of inflammation. C–C chemokine receptor-like 2 (CCRL2), is the other receptor of chemerin, improves the interaction between chemerin and ChemR23. The aim of this study was to evaluate the expression of chemerin and its receptors in gingival tissues with healthy and periodontitis. Tissue biopsy samples were obtained from 20 patients with chronic periodontitis and from the gingiva of 20 healthy individuals undergoing a crown lengthening process. Quantitative real-time PCR (qPCR) was used to examine the mRNA expression of chemerin, ChemR23 and CCRL2. Additionally, protein expression was measured by immunohistochemistry. Both qPCR and immunohistochemistry results revealed that the expression of chemerin and ChemR23 was significantly higher in tissues with periodontitis than in healthy tissues (P = 0.001 and, P = 0.015, respectively). There were no significant differences between healthy tissues and those with periodontitis in terms of mRNA expression of CCRL2, whereas a more intense staining was observed in tissues with periodontitis. The mRNA expression levels of chemerin showed a positive correlation with plaque index, gingival index, probing pocket depth and clinical attachment level (r = 0.448, r = 0.460, r = 0.439 and, r = 0.459, respectively, P < 0.01). To the best of our knowledge, this study is the first to examine the expression of chemerin, ChemR23 and CCRL2 in gingival tissues. Our study suggests that chemerin may play a role in the pathogenesis of periodontitis by causing chemoattraction of immune cells that direct ChemR23 receptors to the site of inflammation.
Similar content being viewed by others
References
Yucel-Lindberg T, Bage T. Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med. 2013;15:e7.
Hans M, Hans VM. Toll-like receptors and their dual role in periodontitis: a review. J Oral Sci. 2011;53(3):263–71.
Krugluger W, Nell A, Solar P, Matejka M, Boltz-Nitulescu G. Influence of sE-selectin and L-selectin on the regulation of cell migration during chronic periodontitis. J Periodontal Res. 1995;30(3):198–203.
Hajishengallis E, Hajishengallis G. Neutrophil homeostasis and periodontal health in children and adults. J Dent Res. 2014;93(3):231–7.
Kim S-R, Jung Y-H, Park H-J, Kim M-K, Jeong J-W, Jang H-O, Yun I, Bae S-K, Bae M-K. Upregulation of thromboxane synthase mediates visfatin-induced interleukin-8 expression and angiogenic activity in endothelial cells. Biochem Biophys Res Commun. 2012;418(4):662–8.
Yoshimura T, Oppenheim JJ. Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. Exp Cell Res. 2011;317(5):674–84.
Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest. 2004;113(9):1318–27.
Mattern A, Zellmann T, Beck-Sickinger AG. Processing, signaling, and physiological function of chemerin. IUBMB Life. 2014;66(1):19–26.
Zabel BA, Kwitniewski M, Banas M, Zabieglo K, Murzyn K, Cichy J. Chemerin regulation and role in host defense. Am J Clin Exp Immunol. 2014;3(1):1–19.
Skrzeczynska-Moncznik J, Wawro K, Stefanska A, Oleszycka E, Kulig P, Zabel BA, Sulkowski M, Kapinska-Mrowiecka M, Czubak-Macugowska M, Butcher EC, et al. Potential role of chemerin in recruitment of plasmacytoid dendritic cells to diseased skin. Biochem Biophys Res Commun. 2009;380(2):323–7.
Nagpal S, Patel S, Jacobe H, DiSepio D, Ghosn C, Malhotra M, Teng M, Duvic M, Chandraratna RA. Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol. 1997;109(1):91–5.
Bondue B, Wittamer V, Parmentier M. Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism. Cytokine Growth Factor Rev. 2011;22(5–6):331–8.
Wittamer V, Bondue B, Guillabert A, Vassart G, Parmentier M, Communi D. Neutrophil-mediated maturation of chemerin: a link between innate and adaptive immunity. J Immunol. 2005;175(1):487–93.
Monnier J, Lewen S, O’Hara E, Huang K, Tu H, Butcher EC, Zabel BA. Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells. J Immunol. 2012;189(2):956–67.
Berg V, Sveinbjörnsson B, Bendiksen S, Brox J, Meknas K, Figenschau Y. Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin21-157. Arthritis Res Ther. 2010;12(6):R228.
Huang K, Du G, Li L, Liang H, Zhang B. Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis. Biomarkers. 2012;17(1):16–20.
Bonomini M, Pandolfi A. Chemerin in renal dysfunction and cardiovascular disease. Vascul Pharmacol. 2016;77:28–34.
Fatima SS, Butt Z, Bader N, Pathan AZ, Hussain S, Iqbal NT. Role of multifunctional chemerin in obesity and preclinical diabetes. Obes Res Clin Pract. 2015;9(5):507–12.
Özcan E, Saygun NI, Serdar MA, Kurt N. Evaluation of the salivary levels of visfatin, chemerin, and progranulin in periodontal inflammation. Clin Oral Invest. 2014;19(4):921–8.
Silness J, Loe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condtion. Acta Odontol Scand. 1964;22:121–35.
Loe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand. 1963;21:533–51.
Consultation WHOE. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157–63.
Kaneko K, Miyabe Y, Takayasu A, Fukuda S, Miyabe C, Ebisawa M, Yokoyama W, Watanabe K, Imai T, Muramoto K, et al. Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritis. Arthritis Res Ther. 2011;13(5):R158.
Buechler C. Chemerin, a novel player in inflammatory bowel disease. Cell Mol Immunol. 2014;11(4):315–6.
Luangsay S, Wittamer V, Bondue B, De Henau O, Rouger L, Brait M, Franssen JD, de Nadai P, Huaux F, Parmentier M. Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. J Immunol. 2009;183(10):6489–99.
Patnaik K, Pradeep AR, Nagpal K, Karvekar S, Singh P, Raju A. Human chemerin correlation in gingival crevicular fluid and tear fluid as markers of inflammation in chronic periodontitis and type-2 diabetes mellitus. J Investig Clin Dent. 2017;8(1):1–7. doi:10.1111/3icd.12181.
Wang N, Wang QJ, Feng YY, Shang W, Cai M. Overexpression of chemerin was associated with tumor angiogenesis and poor clinical outcome in squamous cell carcinoma of the oral tongue. Clin Oral Investig. 2014;18(3):997–1004.
Kukla M, Adamek B, Waluga M, Zalewska-Ziob M, Kasperczyk J, Gabriel A, Mazur W, Sobala-Szczygiel B, Buldak RJ, Zajecki W, et al. Hepatic chemerin and chemokine-like receptor 1 expression in patients with chronic hepatitis C. Biomed Res Int. 2014;2014:517820.
Galligan CL, Matsuyama W, Matsukawa A, Mizuta H, Hodge DR, Howard OM, Yoshimura T. Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis. Arthritis Rheum. 2004;50(6):1806–14.
Mariani F, Roncucci L. Chemerin/chemR23 axis in inflammation onset and resolution. Inflamm Res. 2015;64(2):85–95.
Vermi W, Riboldi E, Wittamer V, Gentili F, Luini W, Marrelli S, Vecchi A, Franssen JD, Communi D, Massardi L, et al. Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. J Exp Med. 2005;201(4):509–15.
Demoor T, Bracke KR, Dupont LL, Plantinga M, Bondue B, Roy MO, Lannoy V, Lambrecht BN, Brusselle GG, Joos GF. The role of ChemR23 in the induction and resolution of cigarette smoke-induced inflammation. J Immunol. 2011;186(9):5457–67.
Otero K, Vecchi A, Hirsch E, Kearley J, Vermi W, Del Prete A, Gonzalvo-Feo S, Garlanda C, Azzolino O, Salogni L, et al. Nonredundant role of CCRL2 in lung dendritic cell trafficking. Blood. 2010;116(16):2942–9.
Muruganandan S, Roman AA, Sinal CJ. Role of chemerin/CMKLR1 signaling in adipogenesis and osteoblastogenesis of bone marrow stem cells. J Bone Miner Res. 2010;25(2):222–34.
Li Y, Shi B, Li S. Association between serum chemerin concentrations and clinical indices in obesity or metabolic syndrome: a meta-analysis. PLoS One. 2014;9(12):e113915.
Neves KB, Cat AND, Lopes RA, Rios FJ, Anagnostopoulou A, Lobato NS, de Oliveira AM, Tostes RC, Montezano AC, Touyz RM. Chemerin regulates crosstalk between adipocytes and vascular cells through Nox. Hypertension. 2015;66(3):657–66.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This study was funded by Gülhane Medical Academy Research Board, with project number AR-2014/36.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Özcan, E., Saygun, N.I., Ilıkçı, R. et al. Evaluation of chemerin and its receptors, ChemR23 and CCRL2, in gingival tissues with healthy and periodontitis. Odontology 106, 29–36 (2018). https://doi.org/10.1007/s10266-017-0297-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10266-017-0297-2