title: Intracellular 3',5'-adenosine cyclic monophosphate level regulates house dust mite-induced interleukin-13 production by T cells from mite-sensitive patients with atopic dermatitis.
abstract: We studied the relationship between cAMP and house dust mite-induced cytokine production in T cells from mite-sensitive patients with atopic dermatitis. T cells from atopic dermatitis patients secreted high level of interleukin-13 (mean 851.1 pg per ml) when cultured with autologous monocytes pulsed with Dermatophagoides pteronyssinus extract. Dermato- phagoides pteronyssinus-induced interleukin-13 secretion was not detected in normal subjects. Adenylate cyclase inhibitor MDL 12,330A and cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram blocked Dermatophagoides pteronyssinus-induced interleukin-13 secretion in atopic dermatitis T cells. In atopic dermatitis T cells, cAMP level rose at 5 min after Dermatophagoides pteronyssinus stimulus then decreased to the basal level at 1 h. MDL 12,330A blocked the Dermatophagoides pteronyssinus-induced cAMP elevation while rolipram blocked its reversal. In atopic dermatitis T cells, adenylate cyclase activity increased at 5 min after Dermatophagoides pteronyssinus stimulus, followed by the increase of cyclic nucleotide phosphodiesterase activity at 15 min. In atopic dermatitis T cells, phospholipase C inhibitor ET-18-OCH3 blocked Dermatophagoides pteronyssinus-induced activation of adenylate cyclase, while rolipram, protein kinase A inhibitor H-89, and MDL 12,330A blocked the activation of cyclic nucleotide phosphodiesterase. These results suggest that Dermatophagoides pteronyssinus may first increase cAMP in atopic dermatitis T cells by activating adenylate cyclase via phospholipase C, and next decrease cAMP by activating cyclic nucleotide phosphodiesterase 4 via protein kinase A, which may be activated by adenylate cyclase-generated cAMP signal. These events are required for interleukin-13 response Dermatophagoides pteronyssinus.
authors.affiliation: Department of Dermatology, Teikyo University, School of Medicine, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Kanda
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000494:pharmacology; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000378:metabolism; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008925:Mites / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D016207:Cytokines; D018793:Interleukin-13; D011948:Receptors, Antigen, T-Cell; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases