title: The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism.
abstract: We investigated and compared the mechanisms by which two dust mite proteolytic allergens, Der p 1 and Der p 3, and a peptide agonist of proteinase-activated receptor 2 (PAR(2)AP) trigger interleukin (IL)-8 release from human pulmonary epithelial cells (A549). Although all three stimuli tested induced the up-regulation of IL-8 (mRNA and protein), the Der p 1-mediated signaling events did not exactly match those induced by PAR(2)AP and Der p 3. First, Der p 1 was less effective in stimulating IL-8 gene transcriptional activity than PAR(2)AP and Der p 3. Second, Der p 1-mediated IL-8 expression was mainly dependent on NF-kappaB, whereas Der p 3 and PAR(2)AP regulated IL-8 expression through the activation of both NF-kappaB and AP-1. Third, although all three MAP kinases, ERK1/2, p38, and JNK, were activated, Der p 1 induced IL-8 release exclusively via the ERK1/2 signaling pathway, whereas PAR(2)AP and Der p 3 also involved the other kinases. Fourth, in HeLa cells, Der p 1 was able to up-regulate IL-8 secretion independent of PAR(2) expression, and in contrast with PAR(2)AP and Der p 3, Der p 1 was unable to affect calcium signaling via PAR(2) in PAR(2)-expressing KNRK cells. Finally, cleavage by Der p 1 of a synthetic peptide representing the N-terminal activation-cleavage site of PAR(2) did not release a high potency activator of PAR(2) as does Der p 3. We conclude that Der p 1 (but not Der p 3)-induced IL-8 production in A549 epithelial cells is independent of PAR(2) activation.
authors.affiliation: Department of Applied Genetics, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, B-6041 Gosselies, Belgium.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Adam
authors.forename: Kristina K
authors.initials: KK
authors.lastname: Hansen
authors.forename: Olaya
authors.initials: O
authors.lastname: Astudillo Fernandez
authors.forename: Olaya Fernandez
authors.initials: OF
authors.lastname: Astudillo
authors.forename: Ludivine
authors.initials: L
authors.lastname: Coulon
authors.forename: Françoise
authors.initials: F
authors.lastname: Bex
authors.forename: Xavier
authors.initials: X
authors.lastname: Duhant
authors.forename: Erika
authors.initials: E
authors.lastname: Jaumotte
authors.forename: Morley D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: Alain
authors.initials: A
authors.lastname: Jacquet
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000096:biosynthesis*; D060829:Arthropod Proteins; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044464:Receptor, PAR-2 / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases; D013997:Time Factors; D014132:Trachea / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000737:chemistry; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D016328:NF-kappa B; D010455:Peptides; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; C451165:Dermatophagoides pteronyssinus antigen p 3; D012697:Serine Endopeptidases; D014357:Trypsin; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1; D002118:Calcium