IL-6 and IL-8 release is mediated via multiple signaling pathways after stimulating dendritic cells with lysophospholipids

Journal of Leukocyte Biology

Yixin Jin¹  Marco Idzko⁵  Johannes Norgauer²  Wolfgang Rüscher⁵  Mirjana Ziemer²  Devrim Öz-Arslan¹  Bassam B. Damaj³  Stephan Sorichter⁵  Daniel Myrtek⁵  Azzam A. Maghazachi⁴ 

[1] Departments of Anatomy and Departments of Anatomy and Departments of Anatomy and;Department of Dermatology, University of Jena, Germany; and Department of Dermatology, University of Jena, Germany; and Department of Dermatology, University of Jena, Germany; and;Bio-Quant, Inc., San Diego, California Bio-Quant, Inc., San Diego, California Bio-Quant, Inc., San Diego, California;Physiology, University of Oslo, Norway; Bio-Quant, Inc., San Diego, California Physiology, University of Oslo, Norway; Physiology, University of Oslo, Norway; Bio-Quant, Inc., San Diego, California Bio-Quant, Inc., San Diego, California Physiology, University of Oslo, Norway; Bio-Quant, Inc., San Diego, CaliforniaDepartment of Pneumology, University of Freiburg, Germany; Department of Pneumology, University of Freiburg, Germany; Department of Pneumology, University of Freiburg, Germany;

关键词: LPA;    S1P;    secretion;    ERK;    PLD;    Rho;    PLC;   

DOI  :  10.1189/jlb.1205751

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive lipid mediators, which are known to play major roles in allergic reactions as well as in tumor pathogenesis. Here, the biological activities and signal pathways of these lysophospholipids (LPLs) in dendritic cells (DCs) were characterized further. Flow cytometric and immunoblot analyses indicate that immature as well as mature DCs express the LPL receptors S1P1, S1P3, S1P5, and LPA2, but not S1P2, S1P4, LPA1, or LPA3. Moreover, enzyme-linked immunosorbent assay experiments demonstrate that simultaneous addition of these LPLs to immature DCs in the presence of lipopolysaccharide enhanced the secretion of the inflammatory cytokines interleukin (IL)-6 and IL-8 in maturing DCs. In contrast, no modification of IL-6 or IL-8 release was observed after exposure of mature DCs to LPLs alone. In addition, studies with pertussis toxin and mitogen-activated protein kinase (MAPK) kinase inhibitor PD98059 suggested that Gi proteins and MAPK pathway are involved in these LPL-induced cell responses. Corroborating these findings, we observed that LPLs induce the phosphorylation of extracellular signal-regulated kinase 1/2 in immature DCs but not in mature DCs. Further analyses show that inhibitors of phosholipase D, Rho, and protein kinase C also inhibited the LPL-induced release of IL-6 and IL-8. Therefore, our findings suggest that lipopolysaccharide in DCs uncouples LPL receptors from the signal-transducing machinery during maturation and that exposure of LPLs at early time-points to maturing DCs modifies the proinflammatory capacity of mature DCs.

【 授权许可】

Unknown