title: IL-32 and IL-17 interact and have the potential to aggravate osteoclastogenesis in rheumatoid arthritis.
abstract: BACKGROUND
  Interleukin (IL)-32 and IL-17 play critical roles in pro-inflammatory responses and are highly expressed in the synovium of patients with rheumatoid arthritis (RA). We investigated the relations between these two cytokines (IL-17 and IL-32) for their ability to induce each other and to stimulate osteoclasts in RA fibroblast-like synoviocytes (FLSs) and T cells.
  
  
  METHODS
  FLSs were isolated through surgical synovectomy obtained from patients with RA or osteoarthritis (OA). Real-time PCR were performed to evaluate the expression of IL-32, IL-17 and osteoclast-related genes. Immunohistochemical staining and tartrate-resistant acid phosphatase (TRAP) staining were performed to determine the distribution of inflammatory cytokines and the presence of osteoclastogenesis.
  
  
  RESULTS
  IL-17 induced the expression of IL-32 in the FLSs from RA patients, as assessed by microarray. IL-32 production was increased by IL-17. IL-32 in the FLSs from RA patients induced the production of IL-17 in CD4+ T cells. IL-32 and IL-17 were colocalized near TRAP-positive areas in joint specimens. IL-17 and IL-32 synergistically induced the differentiation of osteoclasts, as demonstrated by the expression of osteoclast-related genes. IL-32 and IL-17 also could induce resorption by osteoclasts in a RANKL-dependent manner.
  
  
  CONCLUSIONS
  IL-17 affected the expression of IL-32 in FLSs of RA patients and IL-32 induced the production of IL-17 in CD4+ T cells. Both IL-17 and IL-32 cytokines can reciprocally influence each other's production and amplify the function of osteoclastogenesis in the in RA synovium. Separately, IL-17 and IL-32 each stimulated osteoclastogenesis without RANKL. Together, the two cytokines synergistically amplified the differentiation of osteoclasts, independent of RANKL stimulation.
authors.forename: Young-Mee
authors.initials: YM
authors.lastname: Moon
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Yoon
authors.forename: Yang-Mi
authors.initials: YM
authors.lastname: Her
authors.forename: Hye-Joa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Kyoung-Woon
authors.initials: KW
authors.lastname: Kim
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Woo
authors.forename: Kyung-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho-Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D016207:Cytokines; C496971:IL32 protein, human; D020381:Interleukin-17; D007378:Interleukins; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases