title: Upregulated Leptin in Periodontitis Promotes Inflammatory Cytokine Expression in Periodontal Ligament Cells.
abstract: BACKGROUND
  Imbalance or disruption in the expression of inflammatory mediators contributes greatly to the breakdown of the periodontal supporting tissues. Leptin, through binding to its receptor (obesity-related leptin and leptin receptor [OBR]), has potent effects on immunity and inflammation. However, to date, researchers only indicated a role of leptin in periodontitis. No direct or valid evidence exists about how leptin and its receptor are regulated by local inflammation, what effects they have, and the underlying mechanisms.
  
  
  METHODS
  Experimental periodontitis was induced by ligation of mandibular second molars in beagle dogs. The expression of leptin, OBR, and interleukin (IL)-1β was examined by immunohistochemistry. Meanwhile, recombinant human IL-1β was used to stimulate human periodontal ligament cells (hPDLCs) in vitro, and mRNA and protein levels of leptin were measured using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Then, mRNA and protein levels of IL-6 and IL-8 were measured using real-time PCR and ELISA, after stimulation with various concentrations of leptin, knocking down all or only the long form of OBR (OBRb) by small interfering RNA and incubation with multiple intracellular signaling pathway inhibitors, respectively.
  
  
  RESULTS
  Leptin and OBR increased substantially in inflammatory periodontal tissues, which correlated well with the extent of inflammatory infiltration, and was a result of the upregulation in resident cells themselves. A high dose of leptin could induce the expression of mRNA and protein of IL-6 and IL-8 in hPDLCs through binding with OBRb and activating different intracellular signaling pathways.
  
  
  CONCLUSIONS
  Upregulated leptin and OBR in periodontitis stimulated proinflammatory cytokine expression in PDL cells to additionally promote local inflammation.
authors: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.|Department of Periodontology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors: Wei
authors: W
authors: Li
authors: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.|Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.|Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
authors: Baoxin
authors: B
authors: Huang
authors: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
authors: Kaining
authors: K
authors: Liu
authors: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
authors: Jianxia
authors: J
authors: Hou
authors: Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
authors: Huanxin
authors: H
authors: Meng
mesh_terms: D000539:Alveolar Process / Q000737:chemistry; D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003774:Dental Plaque Index; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D005881:Gingiva / Q000737:chemistry; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D020738:Leptin / Q000032:analysis* / Q000235:genetics / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010512:Periodontal Index; D010513:Periodontal Ligament / Q000737:chemistry* / Q000166:cytology; D010518:Periodontitis / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering / Q000235:genetics; D054411:Receptors, Leptin / Q000032:analysis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D020738:Leptin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; D053614:Janus Kinase 2
keywords: Interleukins; leptin; periodontitis; receptors, leptin