Cysteinyl leukotrienes regulate dendritic cell functions in a murine model of asthma.
Dendritic cells (DCs) act as APCs in the airway and play a critical role in allergy. Cysteinyl leukotrienes (cysLTs) synthesized from arachidonic acid are primary mediators of immediate asthmatic reaction. The aim of this study was to investigate the effects of cysLTs on Dermatophagoides farinae (Der f)-pulsed mouse myeloid DCs in inducing allergic airway inflammation in vitro and in vivo. Control DC (medium-pulsed), Der f-pulsed DC, cysLT-pulsed DC, Der f- and cysLT-pulsed DC, and Der f-pulsed and cysLT receptor antagonist (LTRA)-treated DC were prepared from murine bone marrow, and the production of cytokines ws compared. Subsequently, these DCs were intranasally instilled into another group of naive mice, followed by intranasal Der f challenge to induce allergic airway inflammation in vivo. Der f-pulsed DC produced significantly higher amounts of IL-10 and IL-12 compared with control DC. Der f- and cysLT-pulsed DC further increased IL-10 production compared with Der f-pulsed DC. In contrast, treatment of Der f-pulsed DC with LTRA increased IL-12 and decreased IL-10. Intranasal instillation of Der f-pulsed DC resulted in airway eosinophilia associated with a significant rise in IL-5 levels in the airway compared with control DC. Pulmonary eosinophilia and excess IL-5 were further enhanced in Der f- and cysLT-pulsed DC-harboring mice. In contrast, Der f-pulsed and LTRA-treated DC significantly inhibited airway eosinophilia, reduced IL-5, and increased IFN-gamma in the airway. Our results suggest that cysLTs play an important role in the development of allergic airway inflammation by regulating the immunomodulatory functions of DCs.
Machida
Ikuko
I
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Matsuse
Hiroto
H
Kondo
Yuki
Y
Kawano
Tetsuya
T
Saeki
Sachiko
S
Tomari
Shinya
S
Obase
Yasushi
Y
Fukushima
Chizu
C
Kohno
Shigeru
S
D058927:5-Lipoxygenase-Activating Proteins; D000281:Administration, Intranasal; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis / Q000235:genetics; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D003545:Cysteine / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D004195:Disease Models, Animal; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015289:Leukotrienes / Q000008:administration & dosage / Q000096:biosynthesis / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000096:biosynthesis; D018077:Receptors, Leukotriene / Q000096:biosynthesis / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D058927:5-Lipoxygenase-Activating Proteins; C548593:Alox5ap protein, mouse; D039741:Antigens, Dermatophagoides; D002352:Carrier Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D015848:Interleukin-5; D015289:Leukotrienes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; C112381:cysteinyl-leukotriene; D007371:Interferon-gamma; D001094:Arachidonate 5-Lipoxygenase; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; D003545:Cysteine; C083169:leukotriene D4 receptor