Induction of cyclooxygenase-2 expression by allergens in lymphocytes from allergic patients

Chacon Fernandez, Pedro, Vega, Antonio, Monteseirín, Javier, El Bekay, Rajaa, Alba, Gonzalo, Pérez-Formoso, José Luis, Msartínez, Alberto, Asturias, Juan. A., Pérez-Cano, Ramón and Conde, José 2005. Induction of cyclooxygenase-2 expression by allergens in lymphocytes from allergic patients. European Journal of Immunology 35 (8) , pp. 2313-2324. 10.1002/eji.200425572

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Abstract

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of COX-2 expression is responsible for increased PG release during inflammatory conditions and is thought to be also involved in allergic states. In this study, we demonstrate that in human T, B and natural killer lymphocytes from allergic patients, COX-2 expression became induced upon cell challenge with specific allergens and that this process is presumably IgE dependent and occurs after CD23 receptor ligation. This induction took place at both mRNA and protein levels and was accompanied by PGD2 release. IgE-dependent lymphocyte treatment elicited, in parallel, an activation of the MAPK p38 and extracellular signal-regulated kinase 1/2, an enhancement of calcineurin (CaN) activity, and an increase of the DNA-binding activity of the nuclear factor of activated T cells and of NF-κB, with a concomitant decrease in the levels of the cytosolic inhibitor of κB, IκB. In addition, specific chemical inhibitors of MAPK, such as PD098059 and SB203580, as well as MG-132, an inhibitor of proteasomal activity, abolished allergen-induced COX-2 up-regulation, suggesting that this process is mediated by MAPK and NF-κB. However, induction of COX-2 expression was not hampered by the CaN inhibitor cyclosporin A. We also examined the effect of a selective COX-2 inhibitor, NS-398, on cytokine production by human lymphocytes. Treatment with NS-398 severely diminished the IgE-dependently induced production of IL-8 and TNF-α. These results underscore the relevant role of lymphocyte COX-2 in allergy and suggest that COX-2 inhibitors may contribute to the improvement of allergic inflammation through the reduction of inflammatory mediator production by human lymphocytes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	John Wiley & Sons
ISSN:	0014-2980
Last Modified:	28 Jun 2019 02:02
URI:	https://orca.cardiff.ac.uk/id/eprint/65873

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