title: Cigarette smoke condensate extracts induce IL-1-beta production from rheumatoid arthritis patient-derived synoviocytes, but not osteoarthritis patient-derived synoviocytes, through aryl hydrocarbon receptor-dependent NF-kappa-B activation and novel NF-kappa-B sites.
abstract: Cigarette smoking is a major established environmental risk factor for rheumatoid arthritis (RA), and synoviocyte-derived proinflammatory cytokines are implicated in the pathogenesis of RA. We have reported that aryl hydrocarbon or cigarette smoke condensate (CSC) is able to upregulate the production of proinflammatory cytokines from an RA patient-derived synovial fibroblast cell line MH7A. In this study, we compared the effect of CSC on induction of interleukin-1β (IL-1β) from RA or osteoarthritis (OA) patient-derived synovial fibroblasts, and studied the mechanism of the effect of CSC. CSC induced IL-1β mRNA from RA patient-derived synoviocytes and MH7A, but not from OA patient-derived synoviocytes. CSC induced the mRNA and both precursor and mature forms of IL-1β, and caspase-1 activity in MH7A. The mechanism of CSC-induced IL-1β mRNA expression was investigated in MH7A. Reporter gene analyses and promoter pull-down assay indicated that 3 novel NF-κB sites at -3771 to -3762 bp, -3105 to -3096 bp, and -2787 to -2778 bp in the promoter region of the IL-1β gene, especially the far distal NF-κB site and NF-κB activation, are critical for the gene activation by CSC. CSC-induced NF-κB activation, IL-1β promoter activity, IL-1β mRNA upregulation, and CYP1A1 mRNA induction were all inhibited by an aryl hydrocarbon receptor (AhR) antagonist α-naphthoflavone. These results indicate that CSC induced IL-1β production from RA patient-derived synoviocytes, but not OA patient-derived synoviocytes, through AhR-dependent NF-κB activation and novel NF-κB sites.
authors: Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors: Miki
authors: M
authors: Adachi
authors: Shosuke
authors: S
authors: Okamoto
authors: Satomi
authors: S
authors: Chujyo
authors: Tomohiro
authors: T
authors: Arakawa
authors: Megumi
authors: M
authors: Yokoyama
authors: Kyohei
authors: K
authors: Yamada
authors: Aki
authors: A
authors: Hayashi
authors: Kunihiko
authors: K
authors: Akita
authors: Masafumi
authors: M
authors: Takeno
authors: Saotomo
authors: S
authors: Itoh
authors: Takemasa
authors: T
authors: Takii
authors: Yuko
authors: Y
authors: Waguri-Nagaya
authors: Takanobu
authors: T
authors: Otsuka
authors: Kazuichi
authors: K
authors: Hayakawa
authors: Keiji
authors: K
authors: Miyazawa
authors: Kikuo
authors: K
authors: Onozaki
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D014026:Nicotiana / Q000737:chemistry; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012906:Smoke; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D020170:Caspase 1