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Up-regulation of IL-23 p19 expression in human periodontal ligament fibroblasts by IL-1β via concurrent activation of the NF-κB and MAPKs/AP-1 pathways.
Cytokine. 2012 Oct; 60(1):171-8.C

Abstract

Interleukin (IL)-23 is an essential cytokine involved in the expansion of a novel CD4(+) T helper subset known as Th17, which has been implicated in the pathogenesis of periodontitis recently. Our previous study first identified specialized human periodontal ligament fibroblasts (hPDLFs) as an important production source of IL-23. The present study was undertaken to investigate the effects of the pro-inflammatory and Th17-polarizing mediator IL-1β on hPDLFs-mediated IL-23 p19 production, and the molecular mechanism involved. IL-23 p19 expression was in situ detected in IL-1β-stimulated hPDLFs. IL-1β was capable of stimulating the expression of IL-23 p19 mRNA and protein in cultured hPDLFs, which was attenuated by IL-1 receptor antagonist (IL-1Ra) or myeloid differentiation primary response gene 88 (MyD88) inhibitor. Meanwhile, inhibitors of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), activator protein-1 (AP-1), or nuclear factor-kappaB (NF-κB) significantly suppressed IL-23 p19 production from IL-1β-stimulated hPDLFs. Moreover, IL-1β-initiated AP-1 activation was blocked by p38 MAPK, ERK 1/2, or JNK inhibition, whereas NF-κB activity remained unaltered by all the above pathway specific inhibitors. Thus, these results provide evidence that Th17-polarizing mediator IL-1β up-regulated the expression of IL-23 p19 in hPDLFs via NF-κB signaling and MAPKs-dependent AP-1 pathways. Taken together, our findings indicate that IL-1Ra may be used therapeutically to inhibit Th17-driven inflammatory diseases including periodontitis.

Authors+Show Affiliations

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22688014

Citation

Zhu, Lingxin, et al. "Up-regulation of IL-23 P19 Expression in Human Periodontal Ligament Fibroblasts By IL-1β Via Concurrent Activation of the NF-κB and MAPKs/AP-1 Pathways." Cytokine, vol. 60, no. 1, 2012, pp. 171-8.
Zhu L, Wu Y, Wei H, et al. Up-regulation of IL-23 p19 expression in human periodontal ligament fibroblasts by IL-1β via concurrent activation of the NF-κB and MAPKs/AP-1 pathways. Cytokine. 2012;60(1):171-8.
Zhu, L., Wu, Y., Wei, H., Yang, S., Zhan, N., Xing, X., & Peng, B. (2012). Up-regulation of IL-23 p19 expression in human periodontal ligament fibroblasts by IL-1β via concurrent activation of the NF-κB and MAPKs/AP-1 pathways. Cytokine, 60(1), 171-8. https://doi.org/10.1016/j.cyto.2012.05.016
Zhu L, et al. Up-regulation of IL-23 P19 Expression in Human Periodontal Ligament Fibroblasts By IL-1β Via Concurrent Activation of the NF-κB and MAPKs/AP-1 Pathways. Cytokine. 2012;60(1):171-8. PubMed PMID: 22688014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of IL-23 p19 expression in human periodontal ligament fibroblasts by IL-1β via concurrent activation of the NF-κB and MAPKs/AP-1 pathways. AU - Zhu,Lingxin, AU - Wu,Yan, AU - Wei,Hongxia, AU - Yang,Shasha, AU - Zhan,Ni, AU - Xing,Xin, AU - Peng,Bin, Y1 - 2012/06/09/ PY - 2011/12/03/received PY - 2012/05/07/revised PY - 2012/05/17/accepted PY - 2012/6/13/entrez PY - 2012/6/13/pubmed PY - 2013/2/5/medline SP - 171 EP - 8 JF - Cytokine JO - Cytokine VL - 60 IS - 1 N2 - Interleukin (IL)-23 is an essential cytokine involved in the expansion of a novel CD4(+) T helper subset known as Th17, which has been implicated in the pathogenesis of periodontitis recently. Our previous study first identified specialized human periodontal ligament fibroblasts (hPDLFs) as an important production source of IL-23. The present study was undertaken to investigate the effects of the pro-inflammatory and Th17-polarizing mediator IL-1β on hPDLFs-mediated IL-23 p19 production, and the molecular mechanism involved. IL-23 p19 expression was in situ detected in IL-1β-stimulated hPDLFs. IL-1β was capable of stimulating the expression of IL-23 p19 mRNA and protein in cultured hPDLFs, which was attenuated by IL-1 receptor antagonist (IL-1Ra) or myeloid differentiation primary response gene 88 (MyD88) inhibitor. Meanwhile, inhibitors of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), activator protein-1 (AP-1), or nuclear factor-kappaB (NF-κB) significantly suppressed IL-23 p19 production from IL-1β-stimulated hPDLFs. Moreover, IL-1β-initiated AP-1 activation was blocked by p38 MAPK, ERK 1/2, or JNK inhibition, whereas NF-κB activity remained unaltered by all the above pathway specific inhibitors. Thus, these results provide evidence that Th17-polarizing mediator IL-1β up-regulated the expression of IL-23 p19 in hPDLFs via NF-κB signaling and MAPKs-dependent AP-1 pathways. Taken together, our findings indicate that IL-1Ra may be used therapeutically to inhibit Th17-driven inflammatory diseases including periodontitis. SN - 1096-0023 UR - https://www.unboundmedicine.com/medline/citation/22688014/Up_regulation_of_IL_23_p19_expression_in_human_periodontal_ligament_fibroblasts_by_IL_1β_via_concurrent_activation_of_the_NF_κB_and_MAPKs/AP_1_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-4666(12)00212-8 DB - PRIME DP - Unbound Medicine ER -