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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.
J Biol Chem. 2006 Mar 17; 281(11):6910-23.JB

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+Show Affiliations

Department of Applied Genetics, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, B-6041 Gosselies, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16293628

Citation

Adam, Emmanuelle, et al. "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." The Journal of Biological Chemistry, vol. 281, no. 11, 2006, pp. 6910-23.
Adam E, Hansen KK, Astudillo Fernandez O, et al. 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. J Biol Chem. 2006;281(11):6910-23.
Adam, E., Hansen, K. K., Astudillo Fernandez, O., Astudillo, O. F., Coulon, L., Bex, F., Duhant, X., Jaumotte, E., Hollenberg, M. D., & Jacquet, A. (2006). 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. The Journal of Biological Chemistry, 281(11), 6910-23.
Adam E, et al. 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. J Biol Chem. 2006 Mar 17;281(11):6910-23. PubMed PMID: 16293628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Adam,Emmanuelle, AU - Hansen,Kristina K, AU - Astudillo Fernandez,Olaya, AU - Astudillo,Olaya Fernandez, AU - Coulon,Ludivine, AU - Bex,Françoise, AU - Duhant,Xavier, AU - Jaumotte,Erika, AU - Hollenberg,Morley D, AU - Jacquet,Alain, Y1 - 2005/11/17/ PY - 2005/11/19/pubmed PY - 2006/5/11/medline PY - 2005/11/19/entrez SP - 6910 EP - 23 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 281 IS - 11 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/16293628/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_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=16293628 DB - PRIME DP - Unbound Medicine ER -