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Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis
Joint Authors
Dai, Qiaomei
Li, Yang
Yu, Haiyue
Wang, Xiaoyan
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-05-08
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Objectives.
IL-18 is a proinflammatory cytokine with multiple immunoregulatory properties.
We studied the effect of IL-18 gene therapy on the development of murine collagen-induced arthritis (CIA).
Methods.
Plasmid pCAGGS-IL-18 along or in combination with IL-10 or IL-4 was administered to CIA mice.
The incidence and severity of arthritis of the paws were determined by a visual scale.
Joint destruction was determined by histology.
The levels of a panel of cytokines and transcription factors in the synovium were determined by reverse transcription polymerase chain reaction and quantitative RT-PCR.
Quantitative RT-PCR was employed to detect the mRNA expression of TLRs and their pathway on the surface of DCs.
Results.
IL-18 gene therapy had no therapeutic effect on CIA mice.
Additional coadministration with low dosage of recombinant IL-4 ameliorated the disease progression.
Histopathological examination of the joints showed intact cartilage surface in IL-18 gene combined with IL-4-treated mice.
The synovium of IL-18 gene combined with rIL4-treated mice had lower expression of TNF-α, IFN-γ, and IL-17 and higher expression of IL-10.
The mechanism of this response appeared to involve modulation of transcription factors FoxP3 and GATA-3.
The DCs in the spleen and lymph nodes of IL-18 gene combined with rIL4-treated mice had lower expression of TLR2, MyD88, and NF-kB.
Conclusions.
Our findings indicate that pIL-18 gene combined with IL-4 ameliorates arthritis in the CIA mouse by suppression of Th1 and Th17 cytokines and increasing expression of FoxP3 and GATA-3.
The plasmid backbone and multiple immunoregulatory properties of IL-18 appear to play a major role in the pIL-18 coadministration with rIL-4-mediated immunomodulation of arthritis through blocking the TLR2/MyD88/NF-kappa B signaling pathway.
American Psychological Association (APA)
Dai, Qiaomei& Li, Yang& Yu, Haiyue& Wang, Xiaoyan. 2018. Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis. BioMed Research International،Vol. 2018, no. 2018, pp.1-8.
https://search.emarefa.net/detail/BIM-1127125
Modern Language Association (MLA)
Dai, Qiaomei…[et al.]. Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis. BioMed Research International No. 2018 (2018), pp.1-8.
https://search.emarefa.net/detail/BIM-1127125
American Medical Association (AMA)
Dai, Qiaomei& Li, Yang& Yu, Haiyue& Wang, Xiaoyan. Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis. BioMed Research International. 2018. Vol. 2018, no. 2018, pp.1-8.
https://search.emarefa.net/detail/BIM-1127125
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1127125