| First Author | Park E | Year | 2017 |
| Journal | Oncotarget | Volume | 8 |
| Issue | 16 | Pages | 27240-27251 |
| PubMed ID | 28460477 | Mgi Jnum | J:277026 |
| Mgi Id | MGI:6296465 | Doi | 10.18632/oncotarget.15916 |
| Citation | Park E, et al. (2017) Inhibition of lysophosphatidic acid receptor ameliorates Sjogren's syndrome in NOD mice. Oncotarget 8(16):27240-27251 |
| abstractText | Lysophosphatidic acid (LPA), a bioactive lysophospholipid, is involved in the pathogenesis of chronic inflammatory and autoimmune diseases. In this study, we investigated the role of LPA/LPA receptor (LPAR) signaling in the pathogenesis of Sjogren's syndrome (SS). We found that autotaxin, an LPA producing enzyme, and LPAR1 and LPAR3 mRNA, and IL-17 mRNA were highly expressed in the exocrine glands of 20-week-old nonobese diabetic (NOD) mice, which show SS symptoms at this age, as compared with non-symptomatic 8-week-old NOD mice. In an adoptive transfer model using NOD lymphocytes, treatment with Ki16425, an LPAR1/3 antagonist, restored tear and saliva secretion and decreased symptoms of SS compared with the vehicle-treated group. IL-17 levels in serum and lacrimal glands were also significantly reduced by Ki16425 in recipient mice. In addition, Ki16425 treatment of 20-week-old NOD mice, which spontaneously developed SS, restored saliva volume. Treatment of NOD splenocytes with LPA induced the expression of IL-17 in a dose-dependent manner, and Ki16425 inhibited this increase. LPA stimulated the activation of ROCK2 and p38 MAPK; and inhibition of ROCK2 or p38 MAPK suppressed LPA-induced IL-17 expression. Our data suggest that LPAR signaling stimulates SS development by induction of IL-17 production via ROCK and p38 MAPK pathways. Thus, LPAR inhibition could be a possible therapeutic strategy for SS. |
