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
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....
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Online Access: | http://dx.doi.org/10.1155/2018/5164715 |
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doaj-c3aa4025cc5444d2ad9903f1775b14702020-11-24T23:53:27ZengHindawi LimitedBioMed Research International2314-61332314-61412018-01-01201810.1155/2018/51647155164715Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced ArthritisQiaomei Dai0Yang Li1Haiyue Yu2Xiaoyan Wang3Department of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Rheumatology, Qiqihar First Hospital, Qiqihar, ChinaDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaObjectives. 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.http://dx.doi.org/10.1155/2018/5164715 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qiaomei Dai Yang Li Haiyue Yu Xiaoyan Wang |
spellingShingle |
Qiaomei Dai Yang Li Haiyue Yu Xiaoyan Wang 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 |
author_facet |
Qiaomei Dai Yang Li Haiyue Yu Xiaoyan Wang |
author_sort |
Qiaomei Dai |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2018-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2018/5164715 |
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