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Up‐regulation of IL ‐23 expression in human dental pulp fibroblasts by IL ‐17 via activation of the NF ‐κB and MAPK pathways
Author(s) -
Wei L.,
Liu M.,
Xiong H.,
Peng B.
Publication year - 2018
Publication title -
international endodontic journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.988
H-Index - 119
eISSN - 1365-2591
pISSN - 0143-2885
DOI - 10.1111/iej.12871
Subject(s) - mapk/erk pathway , microbiology and biotechnology , p38 mitogen activated protein kinases , kinase , western blot , protein kinase a , signal transduction , chemistry , messenger rna , biology , biochemistry , gene
Aim To investigate the effects of the pro‐inflammatory and Th17‐polarizing mediator IL ‐17 on HDPF s‐mediated IL ‐23 production and the molecular mechanism involved. Methodology Interleukin ( IL )‐17R expression was determined by semi‐quantitative reverse transcriptase‐polymerase chain reaction and Western blot in cultured human dental pulp fibroblasts ( HDPF s). Quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay were used to determine IL ‐23 mRNA and protein levels in IL ‐17‐stimulated HDPF s, respectively. The nuclear factor‐kappa B ( NF ‐κB) and mitogen‐activated protein kinases ( MAPK s) signalling pathways that mediate the IL ‐17‐stimulated production of IL ‐23 was investigated using Western blot and specific signalling inhibitor analyses. Statistical analyses were performed using Kruskal–Wallis tests followed by the Mann–Whitney U ‐test. Statistical significance was considered when the P value < 0.05. Results Primary HDPF s steadily expressed IL ‐17R mRNA and surface‐bound protein. IL ‐17 stimulated the expression of IL ‐23 mRNA and protein in cultured human dental pulp fibroblasts, which was attenuated by IL ‐17 or IL ‐17R neutralizing antibodies. In accordance with the enhanced expression of IL ‐23, IL ‐17 stimulation resulted in rapid activation of p38 MAPK , extracellular signal‐regulated kinase ( ERK ) 1/2, c‐Jun‐N‐terminal kinase ( JNK ) and NF ‐κB in HDPF s. Inhibitors of p38 MAPK , ERK 1/2 or NF ‐κB significantly suppressed, whereas blocking JNK substantially augmented IL ‐23 production from IL ‐17‐stimulated HDPF s. Conclusion HDPF s expressed IL ‐17R and responded to IL ‐17 to produce IL ‐23 via the activation of the NF ‐κB and MAPK signalling pathways. The findings provide insights into the cellular mechanisms of the participation of IL ‐17 in the activation of HDPF s in inflamed pulp tissue.