Toll-Like Receptors Expressed by Synovial Fibroblasts Perpetuate Th1 and Th17 Cell Responses in Rheumatoid Arthritis
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{"title"=>"Toll-like receptors expressed by synovial fibroblasts perpetuate Th1 and Th17 cell responses in rheumatoid arthritis", "type"=>"journal", "authors"=>[{"first_name"=>"Fanlei", "last_name"=>"Hu", "scopus_author_id"=>"25635753800"}, {"first_name"=>"Yingni", "last_name"=>"Li", "scopus_author_id"=>"37661787700"}, {"first_name"=>"Li", "last_name"=>"Zheng", "scopus_author_id"=>"56921036300"}, {"first_name"=>"Lianjie", "last_name"=>"Shi", "scopus_author_id"=>"55751657900"}, {"first_name"=>"Hongjiang", "last_name"=>"Liu", "scopus_author_id"=>"56227194000"}, {"first_name"=>"Xuewu", "last_name"=>"Zhang", "scopus_author_id"=>"15078438400"}, {"first_name"=>"Huaqun", "last_name"=>"Zhu", "scopus_author_id"=>"56030889500"}, {"first_name"=>"Sumei", "last_name"=>"Tang", "scopus_author_id"=>"55878072000"}, {"first_name"=>"Lei", "last_name"=>"Zhu", "scopus_author_id"=>"55635600200"}, {"first_name"=>"Liling", "last_name"=>"Xu", "scopus_author_id"=>"55743776900"}, {"first_name"=>"Yuqin", "last_name"=>"Yang", "scopus_author_id"=>"56227624900"}, {"first_name"=>"Zhanguo", "last_name"=>"Li", "scopus_author_id"=>"55660898400"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84903154906", "sgr"=>"84903154906", "issn"=>"19326203", "pmid"=>"24936783", "doi"=>"10.1371/journal.pone.0100266", "pui"=>"373382249"}, "id"=>"9966b990-c41a-39af-8ec7-83da08d4039d", "abstract"=>"Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone and cartilage erosion. Synovial fibroblast- and T cell-mediated inflammation plays crucial roles in the pathogenesis of RA. However how this inflammation is initiated, propagated, and maintained remains controversial. Here, we systemically examined the contribution of toll-like receptors (TLRs) to the inflammatory mediator production as well as Th1 and Th17 cell hyperactivity in RA. Our results show that rheumatoid arthritis synovial fibroblasts (RASF) express a series of TLRs, including TLR2, TLR3, TLR4, and TLR9, with the predominant expression of TLR3. Moreover, the expression levels of these TLRs were higher than those in osteoarthritis synovial fibroblasts (OASF). Ligation of TLR3, as well as TLR2 and TLR4, resulted in vigorous production of inflammatory cytokines, matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF) in RASF, with activation of the NF-κB, MAPK, and IRF3 pathways. More important, activation of these TLRs expressed by RASF exacerbated inflammatory Th1 and Th17 cell expansion both in cell-cell contact-dependent and inflammatory cytokine-dependent manners, which induced more IFN-γ and IL-17 accumulation. Targeting TLRs may modulate the inflammation in RA and provide new therapeutic strategies for overcoming this persistent disease.", "link"=>"http://www.mendeley.com/research/tolllike-receptors-expressed-synovial-fibroblasts-perpetuate-th1-th17-cell-responses-rheumatoid-arth-2", "reader_count"=>30, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>8, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>3, "Neuroscience"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Canada"=>1, "China"=>1, "Denmark"=>2, "United Kingdom"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1537921"], "description"=>"<p>RASF were stimulated with 10 µg/ml PGN, 25 µg/ml ploy(I:C), 100 ng/mL LPS, or 10 µg/ml CpG for 4 h. Then the cells were harvested for RT-PCR analysis of MMP-1 (A); realtime PCR analyses of MMP-1 (B), MMP-3 (C), MMP-9 (E), and VEGF (F). And also, after stimulation for 24 h, the cell culture supernatants were collected for MMP-3 ELISA (D). The results were presented as mean+SEM of five independent experiments (Wilcoxon signed-rank test, *<i>P</i><0.05 <i>vs.</i> vehicle control).</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "immunology", "Clinical immunology", "Autoimmune diseases", "rheumatoid arthritis", "Immune response", "inflammation", "Immune system", "Innate immune system", "immunity", "Pathology and laboratory medicine", "molecular pathology", "rheumatology", "tlrs", "stimulated", "mmps", "vegf"], "article_id"=>1059996, "categories"=>["Biological Sciences"], "users"=>["Fanlei Hu", "Yingni Li", "Li Zheng", "Lianjie Shi", "Hongjiang Liu", "XueWu Zhang", "Huaqun Zhu", "Sumei Tang", "Lei Zhu", "Liling Xu", "Yuqin Yang", "Zhanguo Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100266.g003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_vLigation_of_TLRs_stimulated_MMPs_and_VEGF_production_in_RASF_/1059996", "title"=>"vLigation of TLRs stimulated MMPs and VEGF production in RASF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-17 03:11:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1537918"], "description"=>"<p>RASF were stimulated with TLR2 agonist PGN (10 µg/ml), TLR3 agonist ploy(I:C) (25 µg/ml), TLR4 agonist LPS (100 ng/mL), or TLR9 agonist CpG (10 µg/ml). 4 h later, the cells were harvested for RT-PCR (A–C, a) and realtime PCR (A–C, b) analyses of IL-6, IL-8, and TNF-α; 24 h later, the cell culture supernatants were collected for ELISA analyses of IL-6, IL-8, and TNF-α (A–C, c). The results were presented as mean+SEM of five independent experiments (Wilcoxon signed-rank test, *<i>P</i><0.05 <i>vs.</i> vehicle control).</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "immunology", "Clinical immunology", "Autoimmune diseases", "rheumatoid arthritis", "Immune response", "inflammation", "Immune system", "Innate immune system", "immunity", "Pathology and laboratory medicine", "molecular pathology", "rheumatology", "agonists", "promoted", "rasf", "inflammatory"], "article_id"=>1059993, "categories"=>["Biological Sciences"], "users"=>["Fanlei Hu", "Yingni Li", "Li Zheng", "Lianjie Shi", "Hongjiang Liu", "XueWu Zhang", "Huaqun Zhu", "Sumei Tang", "Lei Zhu", "Liling Xu", "Yuqin Yang", "Zhanguo Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100266.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR_agonists_promoted_RASF_to_produce_inflammatory_cytokines_/1059993", "title"=>"TLR agonists promoted RASF to produce inflammatory cytokines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-17 03:11:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1537928"], "description"=>"<p>A, RASF were stimulated with 25 µg/ml ploy(I:C) or 100 ng/ml LPS for 24 h, then the expression levels of TSP-1, SDF-1, and IL-15 were determined by realtime PCR analyses (Wilcoxon signed-rank test, *<i>P</i><0.05). B, After activation with 25 µg/ml ploy(I:C) or 100 ng/ml LPS for 24 h, RASF were co-cultured with allogeneic CD4<sup>+</sup> RA patient T cells in the direct contact or the transwell systems for 5 days. Then the T cells were harvested for flow cytometry analysis of the percentage of Th1 and Th17 cells (Wilcoxon signed-rank test, *<i>P</i><0.05). Accordingly, the cell culture supernatants were collected for ELISA analyses of IFN-γ and IL-17 (C) levels (Wilcoxon signed-rank test, *<i>P</i><0.05 <i>vs.</i> unstimulated control). D, RASF/T cell co-culture was performed as described above under Th17 polarization conditions. 5 days later, the cell culture supernatants were collected for IL-17 ELISA (Wilcoxon signed-rank test, *<i>P</i><0.05). The data were shown as mean+SEM of four separate assays.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "immunology", "Clinical immunology", "Autoimmune diseases", "rheumatoid arthritis", "Immune response", "inflammation", "Immune system", "Innate immune system", "immunity", "Pathology and laboratory medicine", "molecular pathology", "rheumatology", "activation", "enhanced", "rasf-mediated", "inflammatory", "th1", "th17"], "article_id"=>1060002, "categories"=>["Biological Sciences"], "users"=>["Fanlei Hu", "Yingni Li", "Li Zheng", "Lianjie Shi", "Hongjiang Liu", "XueWu Zhang", "Huaqun Zhu", "Sumei Tang", "Lei Zhu", "Liling Xu", "Yuqin Yang", "Zhanguo Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100266.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TLR_activation_enhanced_RASF_mediated_inflammatory_Th1_and_Th17_responses_/1060002", "title"=>"TLR activation enhanced RASF-mediated inflammatory Th1 and Th17 responses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-17 03:11:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1537908"], "description"=>"<p>A, The expression of TLRs, including TLR2, TLR3, TLR4, and TLR9 in RASF was detected by RT-PCR analysis. GAPDH was used as the loading control. B, The expression of TLR2, TLR3, TLR4, and TLR9 in RASF (n = 5) and OASF (n = 5) was determined by realtime PCR (Wilcoxon signed-rank test, *<i>P</i><0.05). RASF were stimulated with 25 µg/ml ploy(I:C) for 5 min, 15 min, and 30 min, respectively. Then the cells were harvested and lysised for western blot analysis of p-IκBα (C), p-ERK (D), p-p38 (E), and p-IRF3 (F). β-actin was used as the loading control. The results were representative of at least three experiments.</p>", "links"=>[], "tags"=>["cell biology", "Signal transduction", "cell signaling", "Immunological signaling", "Molecular cell biology", "immunology", "Clinical immunology", "Autoimmune diseases", "rheumatoid arthritis", "Immune response", "inflammation", "Immune system", "Innate immune system", "immunity", "Pathology and laboratory medicine", "molecular pathology", "rheumatology", "tlrs", "excessively"], "article_id"=>1059983, "categories"=>["Biological Sciences"], "users"=>["Fanlei Hu", "Yingni Li", "Li Zheng", "Lianjie Shi", "Hongjiang Liu", "XueWu Zhang", "Huaqun Zhu", "Sumei Tang", "Lei Zhu", "Liling Xu", "Yuqin Yang", "Zhanguo Li"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100266.g001", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_TLRs_were_excessively_expressed_in_RASF_/1059983", "title"=>"Functional TLRs were excessively expressed in RASF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-17 03:11:48"}

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Relative Metric

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