PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells

Abstract

Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium.

CCL26 regulates the proportion of CD4+CD25+FOXP3+�Tregs and the production of inflammatory factors in peripheral blood mononuclear cells following acute ischemic stroke via the STAT5 pathway

“…Tregs have two primary functions, immune response and immunosuppression; they can secrete a variety of anti-inflammatory cytokines and play a key role in inflammation inhibition in immune regulation (8,24). At present, CCL26 is the most selective and active chemotactic agent, which is mainly expressed on the surface of eosinophils, mast cells and Th2 lymphocytes (25). In certain inflammation processes, CCL26 can even promote eosinophil chemotaxis and the recruitment to the inflammatory foci, further promoting degranulation and releasing eosinophil cationic proteins, as well as other cytotoxic substances, which in turn causes a series of inflammatory cascades and finally results in inflammatory damage to brain tissues (26,27).…”

Mitigating Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on Hematopoietic Acute Radiation Syndrome after Total-Body Ionizing Irradiation in Mice

“…As reported elsewhere, it has been shown that PLAG is an effective therapeutic candidate in different inflammatoryassociated diseases, such as rheumatoid arthritis, atopic dermatitis, asthma and hepatitis (20,(34)(35)(36). In addition, the therapeutic efficacy of PLAG has been demonstrated in chemotherapy and radiation-induced oral mucositis in hamster and mouse models, through the effective attenuation of neutrophil infiltration into cheek pouches and tongues and a decrease in inflammatory cytokines (37).…”

“…The chemically synthesized lipid molecule, 1-palmitoyl-2linoleoyl-3-acetyl-rac-glycerol (PLAG), also known as EC-18, is identical to a major constituent found in the antlers of sika deer (19,20). Previously, the therapeutic efficacy of PLAG has been demonstrated in chemotherapy-associated hematopoietic dysfunction (21).…”

1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) attenuates gemcitabine-induced neutrophil extravasation

“…S1B). Migration assay was performed as described previously with minor modifications [24]. Briefly, THP-1 cells were pretreated with various concentrations of PLAG for 1 h and stimulated with gemcitabine for 24 h. The THP-1 supernatant was placed on the bottom chamber as chemoattractant.…”