Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.65 (Der p 1)
 346 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have indicated that the cysteine protease activity of Der p 1 may play a significant role in its ability to elicit IgE antibody responses, mainly through cleavage of membrane CD23 on B cells and interleukin (IL)-4 synthesis and secretion from mast cells and basophils. Here we demonstrate for the first time that Der p 1 also cleaves the alpha subunit of the IL-2 receptor (IL-2R or CD25) from the surface of human peripheral blood T cells and, as a result, these cells show markedly diminished proliferation and interferon gamma secretion in response to potent stimulation by anti-CD3 antibody. Given that the IL-2R is pivotal for the propagation of Th1 cells, its cleavage by Der p 1 may consequently bias the immune response towards Th2 cells, thereby creating an allergic microenvironment.
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PMID:Proteolytic cleavage of CD25, the alpha subunit of the human T cell interleukin 2 receptor, by Der p 1, a major mite allergen with cysteine protease activity. 943 86

House dust mites (HDM) are the most common source of aeroallergens and in genetic susceptible individuals can cause symptoms ranging from atopic dermatitis to bronchial asthma. Der p 1, a major target of the human immune responses to HDM, through its enzymatic properties can modulate the adaptive immune system by the cleavage of CD23 and CD25. The consequences of this would be to promote allergic inflammatory responses. Furthermore, by disrupting epithelial tight junctions Der p 1 facilitates the transport of allergen across the epithelium. Here, we report that Der p 1 has additional effects on the innate defense mechanisms of the lung, by inactivating in vitro and ex vivo the elastase inhibitors human (h) alpha1-proteinase inhibitor (h-A1-Pi), mouse (m-), (but not human [h])-SLPI and h-elafin. We confirm that Der p 1 contain both cysteine and serine proteinases, and extend this finding to demonstrate for the first time that h-elafin is particularly sensitive to the biological activity of the latter. Because these elastase inhibitors have antimicrobial, as well as antielastase activity, our results suggest that inactivation of these innate components of the lung defense system by Der p 1 may increase the susceptibility of patients with allergic inflammation to infection.
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PMID:House dust mite Der p 1 downregulates defenses of the lung by inactivating elastase inhibitors. 1268 23

Several cysteine and serine protease allergens have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6, and Der p 9. A significant body of evidence suggests that these allergens mimic helper T (Th) 2 cell adjuvants. Der p 1 cleaves CD23 from activated B cells and CD25 from T cells. Der p 1 proteolytically degrades tight junctions in lung epithelium and causes release of proinflammatory cytokines from bronchial epithelial cells, mast cells, and basophils. These synergistic effects of mite enzyme allergens may promote IgE synthesis and have direct inflammatory effects on lung epithelium, which could explain why mite allergens are associated with asthma. The crystal structures of the proenzyme and mature forms of Der p 1 have been determined, as have the structures of other indoor allergens that are not enzymes (eg, Der p 2, Fel d 1, and Bla g 2). Cockroach allergens are strongly associated with asthma in US inner cities, yet none of the cockroach allergens that have been cloned are proteolytic enzymes. Thus although mite proteases allergens may act as Th2 adjuvants, a paradoxical effect is that other allergens may elicit strong Th2 responses in the absence of enzyme activity.
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PMID:Proteases as Th2 adjuvants. 1769 45