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Volume 51, Number 1, February 2018

Effects of montelukast on M2-related cytokine and chemokine in M2 macrophages 


Yi-Ching Lin, Ming-Yii Huang, Min-Sheng Lee, Chong-Chao Hsieh, Hsuan-Fu Kuo, Chang-Hung Kuo, Chih-Hsing Hung


 

Corresponding author:

Chang-Hung Kuo, Ta-Kuo Clinic, Number 69, Zihciang 2nd Road, Qianjin District, Kaohsiung 801, Taiwan; Chih-Hsing Hung, Department of Pediatrics, Kaohsiung Medical University Hospital, Number 100, Tz-You 1st Road, Kaohsiung 807, Taiwan. 



 

Background and purpose: 

Asthma is a chronic airway inflammatory disease mediated by T-helper (Th)2 cells. Montelukast (trade name Singulair) is a cysteinyl leukotriene receptor antagonist used for asthma treatment. Mirroring Th1–Th2 polarization, two distinct states of macrophages have been recognized: the classically activated (M1) macrophages and the alternatively activated (M2) macrophages. M2 polarization is known to be a response to the Th2 cytokines; however, the effects of montelukast on M2 macrophages have not been well characterized. The aim of the present study was to investigate the effects of montelukast on the expression of cytokines and chemokines in M2-like macrophages, and to explore possible intracellular signaling pathways.

 



 

Methods:

The human monocytic leukemia cell line THP-1 and human monocytes from healthy donors were cultured with interleukin-4 for M2 polarization, and then the cells were pretreated with or without montelukast before lipopolysaccharide (LPS) stimulation. Supernatants were collected to determine interleukin-10, I-309/CCL1, and MDC/CCL22 levels by enzyme-linked immunosorbent assay. Intracellular signaling was investigated using nuclear factor (NF)-κB inhibitors, mitogen-activated protein kinase (MAPK) inhibitors, and western blot analysis. 



 

Results:

LPS-induced interleukin-10 and I-309/CCL1 expression was significantly suppressed by montelukast in THP-1-derived and human monocyte-derived M2 macrophages after LPS stimulation. MDC/CCL22 expression was only significantly suppressed by montelukast in THP-1-derived M2 macrophages after 48 hours of incubation. In western blot analysis, montelukast was able to suppress LPS-induced MAPK-phospho-p38 and NF-κB-phospho-p65 expression. 



 

Conclusion:

Montelukast suppressed LPS-induced M2-related cytokines and chemokines in alternatively activated macrophages, and the effects might be mediated through the MAPK-p38 and NF-κB-p65 pathways. 



 

Key words:

Chemokine, M2 macrophage, Mitogen-activated protein kinase, Montelukast, Nuclear factor-κB