Anti-inflammatory effects of the prostacyclin analogue iloprost in an in vitro model of inflamed human dental pulp cells
Rahman Wahyudi DDS
Faculty of Dentistry, Graduate Program in Oral Biology, Chulalongkorn University, Bangkok, Thailand
Search for more papers by this authorSonntana Seang DDS, PhD
Faculty of Dentistry, Graduate Program in Oral Biology, Chulalongkorn University, Bangkok, Thailand
Department of Oral and Maxillofacial Surgery and Dentistry, Khmer-Soviet Friendship Hospital, Phnom Penh, Cambodia
Search for more papers by this authorVincent Everts PhD
Faculty of Dentistry, University of Amsterdam and Vrije University Amsterdam, Amsterdam, The Netherlands
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Search for more papers by this authorThanaphum Osathanon DDS, PhD
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Search for more papers by this authorCorresponding Author
Chalida Nakalekha Limjeerajarus DDS, PhD
Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Correspondence
Chalida Nakalekha Limjeerajarus, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Email: [email protected]
Search for more papers by this authorRahman Wahyudi DDS
Faculty of Dentistry, Graduate Program in Oral Biology, Chulalongkorn University, Bangkok, Thailand
Search for more papers by this authorSonntana Seang DDS, PhD
Faculty of Dentistry, Graduate Program in Oral Biology, Chulalongkorn University, Bangkok, Thailand
Department of Oral and Maxillofacial Surgery and Dentistry, Khmer-Soviet Friendship Hospital, Phnom Penh, Cambodia
Search for more papers by this authorVincent Everts PhD
Faculty of Dentistry, University of Amsterdam and Vrije University Amsterdam, Amsterdam, The Netherlands
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Search for more papers by this authorThanaphum Osathanon DDS, PhD
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Dental Stem Cell Biology Research Unit, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Search for more papers by this authorCorresponding Author
Chalida Nakalekha Limjeerajarus DDS, PhD
Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Center of Excellence in Genomics and Precision Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
Correspondence
Chalida Nakalekha Limjeerajarus, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Email: [email protected]
Search for more papers by this authorAbstract
Iloprost's anti-inflammatory effects on human dental pulp stem cells (HDPCs) are currently unknown. We hypothesized that iloprost could downregulate the expression of inflammatory-related genes and protein in an inflamed HDPC in vitro model. To induce inflammation, the HDPCs were treated with a cocktail of interleukin-1 beta, interferon-gamma, and tumour necrosis alpha, at a ratio of 1:10:100. Iloprost (10−6 M) was then added or not to the cultures. Interleukin-6 (IL-6) and interleukin-12 (IL-12) mRNA expression were assessed by real-time polymerase chain reaction. IL-6 protein expression was assessed by enzyme-linked immunosorbent assay. The results were analysed using one-way ANOVA or the Kruskal–Wallis test. The cytokine cocktail induced more robust IL-6 expression than LPS treatment. Iloprost slightly, yet significantly, downregulated IL-6 and IL-12 mRNA expression. These findings suggest that iloprost might be used as a beneficial component in vital pulp therapy.
CONFLICT OF INTEREST STATEMENT
The authors deny any conflict of interest. The authors do not have any financial interest in the companies whose materials are included in this article.
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REFERENCES
- 1Janebodin K, Horst OV, Osathanon T. Dental pulp response to pulp capping materials and bioactive molecules. CU Dent J. 2010; 33: 229–48.
- 2Dammaschke T, Galler K, Krastl G. Current recommendations for vital pulp treatment. Dtsch Zahnärztl Z Int. 2019; 1: 43–52.
- 3Zaky S, Shehabeldin M, Ray H, Sfeir C. The role of inflammation modulation in dental pulp regeneration. Eur Cell Mater. 2021; 41: 184–93.
- 4Kuzushima M, Mogi M, Togari A. Cytokine-induced nitric-oxide-dependent apoptosis in mouse osteoblastic cells: involvement of p38MAP kinase. Arch Oral Biol. 2006; 51(11): 1048–53.
- 5Sidney LE, Kirkham GR, Buttery LD. Comparison of osteogenic differentiation of embryonic stem cells and primary osteoblasts revealed by responses to IL-1β, TNF-α, and IFN-γ. Stem Cells Dev. 2014; 23(6): 605–17.
- 6Gryglewski R, Szczeklik A. Prostacyclin and atherosclerosis. In: AGB Kovach, J Hamar, L Szabo, editors. Cardiovascular physiology: microcirculation and capillary exchange. Amsterdam (NLD): Elsevier; 1981. p. 55–64.
10.1016/B978-0-08-026819-4.50008-8 Google Scholar
- 7Olschewski H, Rohde B, Behr J, Ewert R, Gessler T, Ghofrani HA, et al. Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension. Chest. 2003; 124(4): 1294–304.
- 8Zhou W, Hashimoto K, Goleniewska K, O'Neal JF, Ji S, Blackwell TS, et al. Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells. J Immunol. 2007; 178(2): 702–10.
- 9Birukova AA, Wu T, Tian Y, Meliton A, Sarich N, Tian X, et al. Iloprost improves endothelial barrier function in lipopolysaccharide-induced lung injury. Eur Respir J. 2013; 41(1): 165–76.
- 10Müller T, Dürk T, Blumenthal B, Herouy Y, Sorichter S, Grimm M, et al. Iloprost has potent anti-inflammatory properties on human monocyte-derived dendritic cells. Clin Exp Allergy. 2010; 40(8): 1214–21.
- 11Limjeerajarus CN, Osathanon T, Manokawinchoke J, Pavasant P. Iloprost up-regulates vascular endothelial growth factor expression in human dental pulp cells in vitro and enhances pulpal blood flow in vivo. J Endod. 2014; 40(7): 925–30.
- 12Seang S, Pavasant P, Limjeerajarus CN. Iloprost induces dental pulp angiogenesis in a growth factor–free 3-dimensional organ culture system. J Endod. 2018; 44(5): 759–64.e2.
- 13Seang S, Pavasant P, Everts V, Limjeerajarus CN. Prostacyclin analog promotes human dental pulp cell migration via a matrix metalloproteinase 9–related pathway. J Endod. 2019; 45(7): 873–81.
- 14Jearanaiphaisarn T, Sanharati T, Pavasant P, Nakalekha Limjeerajarus C. The effect of iloprost on cell proliferation and angiogenesis-related gene expression in human periodontal ligament cells. Odontology. 2018; 106(1): 11–8.
- 15de Souza AP, Vale VLC, Silva MC, de Oliveira Araújo IB, Trindade SC, Moura-Costa LF, et al. MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection. BMC Microbiol. 2014; 14(1): 230.
- 16Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2(1): 1–9.
- 17Tokuda M, Miyamoto R, Sakuta T, Nagaoka S, Torii M. Substance P activates p38 mitogen-activated protein kinase to promote IL-6 induction in human dental pulp fibroblasts. Connect Tissue Res. 2005; 46(3): 153–8.
- 18Kim Y-S, Min K-S, Lee S-I, Shin S-J, Shin K-S, Kim E-C. Effect of proinflammatory cytokines on the expression and regulation of human beta-defensin 2 in human dental pulp cells. J Endod. 2010; 36(1): 64–9.
- 19Giuroiu CL, Vataman M, Melian G, Bularda D, Lozneanu L, Salceanu M, et al. Detection and assessment of interleukin 6 in irreversible pulp inflamation. Rev Chim. 2017; 68(2): 323–7.
- 20Hahn C-L, Best AM, Tew JG. Cytokine induction by Streptococcus mutans and pulpal pathogenesis. Infect Immun. 2000; 68(12): 6785–9.
- 21Yang S-K, Wang Y-C, Chao C-C, Chuang Y-J, Lan C-Y, Chen B-S. Dynamic cross-talk analysis among TNF-R, TLR-4 and IL-1R signalings in TNFα-induced inflammatory responses. BMC Med Genomics. 2010; 3(1): 1–19.
- 22Schmitz ML, Weber A, Roxlau T, Gaestel M, Kracht M. Signal integration, crosstalk mechanisms and networks in the function of inflammatory cytokines. Biochim Biophys Acta. 2011; 1813(12): 2165–75.
- 23Wesemann DR, Benveniste EN. STAT-1α and IFN-γ as modulators of TNF-α signaling in macrophages: regulation and functional implications of the TNF receptor 1: STAT-1α complex. J Immunol. 2003; 171(10): 5313–9.
- 24Barkhordar R, Hayashi C, Hussain M. Detection of interleukin-6 in human dental pulp and periapical lesions. Dent Traumatol. 1999; 15(1): 26–7.
- 25Wright HL, Cross AL, Edwards SW, Moots RJ. Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo. Rheumatology. 2014; 53(7): 1321–31.
- 26Gabay C. Interleukin-6 and chronic inflammation. Arthritis Res Ther. 2006; 8(2): 1–6.
- 27Schett G. Physiological effects of modulating the interleukin-6 axis. Rheumatology. 2018; 57(Suppl 2): ii43–50.
- 28Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius A. Molecular mechanisms of interleukin-10-mediated inhibition of NF-κB activity: a role for p50. Clin Exp Immunol. 2004; 135(1): 64–73.
- 29Limjeerajarus CN, Chanarattanubol T, Trongkij P, Rujiwanichkul M, Pavasant P. Iloprost induces tertiary dentin formation. J Endod. 2014; 40(11): 1784–90.
- 30Lee WS, Yang H, Chon HJ, Kim C. Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity. Exp Mol Med. 2020; 52(9): 1475–85.