title: A Major Human Oral Lysophosphatidic Acid Species, LPA 18:1, Regulates Novel Genes in Human Gingival Fibroblasts.
abstract: BACKGROUND
  The small bioactive lipid lysophosphatidic acid (LPA) plays critical roles in both normal physiology and inflammation in many systems. However, its actions are just beginning to be defined in oral biology and pathophysiology.
  
  
  METHODS
  Microarray analysis was used to test the hypothesis that human gingival fibroblasts (GFs) would show significant changes in wound-healing and inflammation-related gene transcripts in response to a major human salivary and gingival crevicular fluid LPA species, 18:1, and that they would express transcript for the major LPA-producing enzyme autotaxin. The microarray results were validated for three highly relevant upregulated inflammatory transcripts using quantitative reverse transcription-polymerase chain reaction (QRT-PCR). Liquid chromatography-tandem mass spectrometry was used to assay time-dependent LPA species production by GFs.
  
  
  RESULTS
  LPA 18:1 significantly regulated 20 GF novel and 27 known genes linked to the control of inflammation (P ≤0.01). QRT-PCR validation of interleukin (IL)-8, IL-11, and suppressor of cytokine signaling 2 (SOCS2) messenger RNAs confirmed statistically significant differences from control (P ≤0.05). Autotaxin transcript was present, and GFs were found to produce multiple LPA species in a time-dependent manner.
  
  
  CONCLUSIONS
  The upregulation of transcripts for known GF proinflammatory (IL-6, IL-8) and anti-inflammatory (IL-11) ILs, along with SOCS2, shows that LPA transiently regulates a complex set of GF genes critical to periodontal wound healing and inflammation. These results implicate LPA exerting actions on GFs that are compatible with functioning as a mediator in oral fibroblast biology and inflammatory responses. Therefore, LPA may potentially modulate/regulate periodontal inflammation.
authors: Department of Oral Biology, Creighton University School of Dentistry, Omaha, NE.
authors: D Roselyn
authors: DR
authors: Cerutis
authors: Michael D
authors: MD
authors: Weston
authors: Yazen
authors: Y
authors: Alnouti
authors: Sai P
authors: SP
authors: Bathena
authors: Martha E
authors: ME
authors: Nunn
authors: Afolabi O
authors: AO
authors: Ogunleye
authors: Timothy P
authors: TP
authors: McVaney
authors: Karmel V
authors: KV
authors: Headen
authors: Takanari
authors: T
authors: Miyamoto
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000166:cytology* / Q000187:drug effects; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000235:genetics; D018836:Inflammation Mediators / Q000032:analysis; D017370:Interleukin-11 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D010727:Phosphoric Diester Hydrolases / Q000032:analysis; D012463:Saliva / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D000099189:Lysophospholipase D
chemical_list: D018836:Inflammation Mediators; D017370:Interleukin-11; D015850:Interleukin-6; D016209:Interleukin-8; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D050826:Suppressor of Cytokine Signaling Proteins; D000099189:Lysophospholipase D; C508606:CXCL8 protein, human; C508611:IL11 protein, human; C508600:IL6 protein, human; C106643:SOCS2 protein, human; C032881:lysophosphatidic acid
keywords: Cytokines; fibroblasts; gene expression; humans; inflammation; lysophospholipids