PMID- 16771778 OWN - NLM STAT- MEDLINE DCOM- 20060809 LR - 20211203 IS - 0905-6157 (Print) IS - 0905-6157 (Linking) VI - 17 IP - 4 DP - 2006 Jun TI - Effects of leukotriene receptor antagonists on monocyte chemotaxis, p38 and cytoplasmic calcium. PG - 250-8 AB - Montelukast and zafirlukast, two cysteinyl leukotriene receptor antagonists (LTRAs), have been shown to have a beneficial effect on the clinical symptoms of asthma. LTRAs can inhibit eosinophil recruitment; however, little is known about their role in monocyte migration. We investigated whether montelukast and zafirlukast could suppress chemokine-induced chemotaxis of monocytes and signaling. Chemotaxis of monocytes from peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs), and THP-1 cells was evaluated using a 24-well transwell microchamber. [Ca2+]i was measured with the fluorescence calcium indicator fura-2/AM photometry system. p38 MAPK expression was measured by Western blotting. Results showed that montelukast (1-100 microm) and zafirlukast (100 microm) significantly down-regulated monocyte chemoattractant protein-1(MCP-1)-induced chemotaxis of THP-1 cells and human primary monocytes from PBMCs and CBMCs (p<0.05, each comparison). Montelukast also abolished MCP-1-induced [Ca2+]i and pp38 MAPK expression in THP-1 cells in a dose-dependent manner. These data demonstrate that montelukast is effective in down-regulating human monocyte chemotaxis induced by MCP-1. This effect may involve the down-regulation of MCP-1-induced [Ca2+]i and p38 MAPK expression. FAU - Hung, Chih-Hsing AU - Hung CH AD - Department of Pediatrics, Tri-service General Hospital, National Defense Medical Center, Taipei, and Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University, Taiwan, Republic of China. pedhung@kmu.edu.fw FAU - Li, Chi-Yuan AU - Li CY FAU - Hua, Yi-Ming AU - Hua YM FAU - Chen, Chun-Jung AU - Chen CJ FAU - Yang, Kuender D AU - Yang KD FAU - Jong, Yuh-Jyh AU - Jong YJ LA - eng PT - Journal Article PL - England TA - Pediatr Allergy Immunol JT - Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology JID - 9106718 RN - 0 (Acetates) RN - 0 (Anti-Asthmatic Agents) RN - 0 (Cyclopropanes) RN - 0 (Indoles) RN - 0 (Leukotriene Antagonists) RN - 0 (Phenylcarbamates) RN - 0 (Quinolines) RN - 0 (Sulfides) RN - 0 (Sulfonamides) RN - 0 (Tosyl Compounds) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - MHM278SD3E (montelukast) RN - SY7Q814VUP (Calcium) RN - XZ629S5L50 (zafirlukast) SB - IM MH - Acetates/pharmacology MH - Anti-Asthmatic Agents/*pharmacology MH - Blotting, Western MH - Calcium/*metabolism MH - Cell Separation MH - Chemotaxis/*drug effects MH - Cyclopropanes MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Fetal Blood MH - Flow Cytometry MH - Humans MH - Indoles MH - Intracellular Fluid/drug effects/metabolism MH - Leukotriene Antagonists/*pharmacology MH - Monocytes/*drug effects/enzymology/metabolism MH - Phenylcarbamates MH - Photometry MH - Pregnancy MH - Quinolines/pharmacology MH - Reference Values MH - Sulfides MH - Sulfonamides MH - Time Factors MH - Tosyl Compounds/pharmacology MH - p38 Mitogen-Activated Protein Kinases/*drug effects/metabolism EDAT- 2006/06/15 09:00 MHDA- 2006/08/10 09:00 CRDT- 2006/06/15 09:00 PHST- 2006/06/15 09:00 [pubmed] PHST- 2006/08/10 09:00 [medline] PHST- 2006/06/15 09:00 [entrez] AID - PAI385 [pii] AID - 10.1111/j.1399-3038.2006.00385.x [doi] PST - ppublish SO - Pediatr Allergy Immunol. 2006 Jun;17(4):250-8. doi: 10.1111/j.1399-3038.2006.00385.x.