Cysteinyl leukotriene receptor 1 mediates LTD4-induced activation of mouse microglial cells in vitro

Abstract

Aim: To investigate the roles of cysteinyl leukotriene receptors CysLT 1 R and CysLT 2 R in leukotriene D 4 (LTD 4 )-induced activation of microglial cells in vitro. Methods: Mouse microglial cell line BV2 was transfected with pcDNA3.1(+)-hCysLT 1 R or pcDNA3.1(+)-hCysLT 2 R. The expression of relevant mRNAs and proteins in the cells was detected using RT-PCR and Western blotting, respectively. Phagocytosis was determined with flow cytometry analysis. The release of interleukin-1β (IL-1β) from the cells was measured using an ELISA assay. Results: The expression of CysLT 1 R or CysLT 2 R was considerably increased in the transfected BV2 cells, and the receptors were mainly distributed in the plasma membrane and cytosol. Treatment of the cells expressing CysLT 1 R or CysLT 2 R with CysLT receptor agonist LTD 4 (0.1-100 nmol/L) concentration-dependently enhanced the phagocytosis, and increased mRNA expression and release of IL-1β. Moreover, the responses of hCysLT 1 R-BV2 cells to LTD 4 were significantly larger than those of hCysLT 2 R-BV2 or WT-BV2 cells. Pretreatment of hCysLT 1 R-BV2 cells with the selective CysLT 1 R antagonist montelukast (1 μmol/L) significantly blocked LTD 4 -induced phagocytosis as well as the mRNA expression and release of IL-1β, whereas the selective CysLT 2 R antagonist HAMI 3379 (1 μmol/L) had no such effects. Conclusion: CysLT 1 R mediates LTD 4 -induced activation of BV2 cells, suggesting that CysLT 1 R antagonists may exert anti-inflammatory activity in brain diseases.

CysLT1 Receptor Is Protective against Oxidative Stress in a Model of Irritant-Induced Asthma

“…Whether this marked upregulation leads to a greater neutrophilia or is secondary to the recruitment of neutrophils is not clear, but the lack of comparable increases in lta4h expression suggests that the findings are not attributable simply to neutrophil recruitment. Additionally, reduced efferocytosis of neutrophils by macrophages is suggested by in vitro studies that have shown that cysLT 1 R antagonists inhibit phagocytic activity, whereas overexpression of cysLT 1 R enhances phagocytosis (48). In vivo, alveolar macrophages in CysLTr1 2/2 mice exhibit impaired phagocytic activity (49), and sPLA2-dependent cysLT generation partially mediates macrophage phagocytic activity in a model of immune erosive inflammatory arthritis (50).…”

6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer’s disease via CysLT1R-mediated inhibition of cathepsin B

“…CysLTs act on at least two G protein-coupled receptors, CysLT1R and CysLT2R, which mediate various responses in the peripheral and central nervous systems [5]. In more recent years, focus has intensified on CysLT1R and its antagonists, since this receptor has been shown to have a novel pathophysiological role in brain damage [7].…”

“…CysLTs activate their corresponding receptors, such as the CysLT1 receptor (CysLT1R) and CysLT2 receptor [4], which mediate various responses in the peripheral and central nervous systems [5,6]. Moreover, CysLT1R is expressed in neurons and glial-appearing cells in brains after traumatic injury [7].…”

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

“…CysLTR-1 [26], whose expression is normally lower than the CysLTR-2 one [1, 3], is localized in microvascular endothelial cells [21], in glial cells, and in several types of neuronal cells [15, 27, 28]. …”