A Major Human Oral Lysophosphatidic Acid Species, LPA 18:1, Regulates Novel Genes in Human Gingival Fibroblasts
| Autor: | Sai Praneeth Reddy Bathena, Afolabi O. Ogunleye, Michael D. Weston, D. Roselyn Cerutis, Karmel V. Headen, Yazen Alnouti, Martha E. Nunn, Timothy P. McVaney, Takanari Miyamoto |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Transcription Genetic Microarray Gingiva Suppressor of Cytokine Signaling Proteins Inflammation Biology chemistry.chemical_compound Downregulation and upregulation Gene expression Lysophosphatidic acid medicine Humans Saliva Gene Cells Cultured Interleukin-6 Phosphoric Diester Hydrolases Microarray analysis techniques Interleukin-8 Gingival Crevicular Fluid Fibroblasts Interleukin-11 Molecular biology Gene Expression Regulation chemistry Periodontics Female lipids (amino acids peptides and proteins) Inflammation Mediators Lysophospholipids medicine.symptom Autotaxin Signal Transduction |
| Zdroj: | Journal of Periodontology. 86:713-725 |
| ISSN: | 1943-3670 0022-3492 |
| DOI: | 10.1902/jop.2015.140592 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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