Henderson et al have demonstrated that montelukast blockade

Henderson et al. have demonstrated that montelukast blockade of CysLT1 receptors improves airway remodeling, including airway goblet cell metaplasia, smooth muscle cell layer thickening, and subepithelial fibrosis in a mouse model of asthma. The histological findings of this study revealed a thickened bronchial epithelium exhibiting epithelial cells filled with AB/PAS-positive mucus in the specimens prepared from the fccp mg patients. Interestingly, in these specimens, CysLT1 receptors tended to be expressed on the mucus-positive epithelium, suggesting that CysLT1 receptors activation is involved in the development of epithelial remodeling in humans as reported in mice. It has also been reported that CysLTs mediate Th2 cell-dependent pulmonary inflammation through activation of CysLT1 receptors in mice.27, 28 Considering the fact that both CysLT2 and CysLT1 receptors are highly expressed in the airway epithelium, it is possible that CysLT2 receptors also play a role in the development of airway remodeling. This hypothesis need to be further investigated both in vitro and in vivo. In conclusion, we have shown in this study that CysLT2 receptors were expressed in lung specimens isolated from 2 asthma subjects. This CysLT2 receptors expression may contribute to antigen-induced bronchoconstriction in certain asthma cases. These results imply that CysLT2 receptor antagonists, including BayCysLT2RA and ONO-6950, may be useful for the treatment of the certain asthma population. However, because the present findings were led from only 2 asthma specimens, further preclinical and clinical studies on CysLT2-or CysLT1/2-receptor antagonists are required.
Acknowledgments
Introduction Microglia are the primary immune cells of the brain. They are rapidly activated in response to various pathological conditions such as infection, stroke or neurodegenerative processes. Increased production of proinflammatory cytokines by activated microglia contributes to microglia-related neurotoxicity in a series of neurodegenerative disorders, including Parkinson׳s disease (PD) (Glass et al., 2010, More et al., 2013, Nolan et al., 2013, Ramsey and Tansey, 2014). Inhibition or blockade of microglial activation was shown to attenuate nigrostriatal inflammation and to rescue dopaminergic neurons from degeneration in experimental PD (Glass et al., 2010, Ramsey and Tansey, 2014, Tansey and Goldberg, 2010). Therefore, identification of the molecules that modulate microglial activation and release of proinflammatory mediators may offer a potential therapeutic strategy for the treatment of PD. Cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators closely associated with cerebral ischemic injury. CysLTs induce inflammatory responses mediated by at least two different CysLT receptors (CysLT1R and CysLT2R) (Bäck et al., 2011, Singh et al., 2010). It has been reported that the CysLT1R plays important regulatory roles in cerebral ischemic injury, and CysLT1R selective antagonists pranlukast and montelukast have protective effects on cerebral ischemia (Fang et al., 2006, Yu et al., 2005, Yu et al., 2014, Zhang and Wei, 2003, Zhang et al., 2013, Zhao et al., 2011b). Compared to CysLT1Rs, the roles of CysLT2Rs remain largely unexplored due to the lack of selective CysLT2R antagonists (other than the nonselective CysLT1R/CysLT2R antagonist Bay U9773). Recently, HAMI 3379 has been reported to be a selective antagonist for CysLT2R (Wunder et al., 2010). Several recent studies have found that CysLT2R is involved in postischemic inflammation and brain injury in focal cerebral ischemia of rat as well as in ischemic-like injury induced by oxygen-glucose deprivation (OGD) in vitro, and the antagonism of CysLT2R by HAMI 3379 protects neurons against ischemic brain injury (Shi et al., 2012, Shi et al., 2015, Zhao et al., 2011a, Zhang et al., 2013). However, whether CysLT2Rs mediate PD-associated microglial inflammation and microglia-dependent neurotoxicity remains unclear.