PMID- 15356554 OWN - NLM STAT- MEDLINE DCOM- 20041020 LR - 20131121 IS - 0091-6749 (Print) IS - 0091-6749 (Linking) VI - 114 IP - 3 DP - 2004 Sep TI - Effects of antiasthmatic agents on the functions of peripheral blood monocyte-derived dendritic cells from atopic patients. PG - 538-44 AB - BACKGROUND: Dendritic cells (DCs), the antigen-presenting cells in the airway, play a critical role in asthma. Nevertheless, there is little information on the effects of antiasthmatic agents on DCs. OBJECTIVES: The purpose of the present study was to determine the effects of representative antiasthmatic agents, including cysteinyl leukotriene (cysLT) 1 receptor antagonists, corticosteroid, and tacrolimus, on DCs in inducing allergy. METHODS: Human peripheral blood monocyte-derived DCs (MoDCs) generated from atopic and healthy subjects were pulsed with Dermatophagoides farinae allergen in the presence of medium alone, pranlukast, montelukast, dexamethasone, or tacrolimus. The mRNA expressions of cysLT receptor, cysLTs producing enzymes, and various surface markers on MoDCs, as well as the concentrations of cysLTs, IL-10, and IL-12 in cultured supernatants, were determined. MoDCs were also cocultured in vitro with autologous CD4(+) T cells, and IL-5 and IFN-gamma production was measured. RESULTS: MoDCs of atopic patients expressed mRNAs of cysLT1 receptor and cysLT-producing enzymes, and allergen pulsing significantly increased cysLT production. MoDCs of atopic patients showed a T(H)2-favoring phenotype and induced T(H)2-skewed cytokine production from autologous CD4(+) T cells. Dexamethasone and tacrolimus inhibited allergen-pulsed MoDC-induced cytokine production by autologous CD4(+) T cells without and with IL-10 inhibition, respectively. CysLT1 receptor antagonists had no effect on MoDC functions. CONCLUSION: Our results indicate that MoDCs of atopic patients induce a T(H)2 reaction. Corticosteroid and tacrolimus, but not cysLT1 receptor antagonists, inhibit T(H)2 reactions, and this effect is probably mediated through different pathways. FAU - Saeki, Sachiko AU - Saeki S AD - Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan. FAU - Matsuse, Hiroto AU - Matsuse H FAU - Kondo, Yuki AU - Kondo Y FAU - Machida, Ikuko AU - Machida I FAU - Kawano, Tetsuya AU - Kawano T FAU - Tomari, Shinya AU - Tomari S FAU - Obase, Yasushi AU - Obase Y FAU - Fukushima, Chizu AU - Fukushima C FAU - Kohno, Shigeru AU - Kohno S LA - eng PT - Journal Article PL - United States TA - J Allergy Clin Immunol JT - The Journal of allergy and clinical immunology JID - 1275002 RN - 0 (Adrenal Cortex Hormones) RN - 0 (Anti-Asthmatic Agents) RN - 0 (Antigens, Dermatophagoides) RN - 0 (Cytokines) RN - 0 (Leukotriene Antagonists) RN - 0 (Leukotrienes) RN - 0 (cysteinyl-leukotriene) RN - K848JZ4886 (Cysteine) RN - WM0HAQ4WNM (Tacrolimus) SB - IM MH - Adrenal Cortex Hormones/administration & dosage/pharmacology MH - Adult MH - Anti-Asthmatic Agents/*pharmacology/therapeutic use MH - Antigens, Dermatophagoides/immunology MH - CD4-Positive T-Lymphocytes/immunology/metabolism MH - Cell Differentiation MH - Cysteine/metabolism MH - Cytokines/metabolism MH - Dendritic Cells/*drug effects MH - Female MH - Humans MH - Hypersensitivity, Immediate/*drug therapy/immunology MH - Leukotriene Antagonists/administration & dosage/pharmacology MH - Leukotrienes/metabolism MH - Male MH - Monocytes/*cytology MH - Tacrolimus/administration & dosage/pharmacology EDAT- 2004/09/10 05:00 MHDA- 2004/10/22 09:00 CRDT- 2004/09/10 05:00 PHST- 2004/09/10 05:00 [pubmed] PHST- 2004/10/22 09:00 [medline] PHST- 2004/09/10 05:00 [entrez] AID - S0091674904015672 [pii] AID - 10.1016/j.jaci.2004.05.053 [doi] PST - ppublish SO - J Allergy Clin Immunol. 2004 Sep;114(3):538-44. doi: 10.1016/j.jaci.2004.05.053.