Expression of cyclooxygenase-2 and 5-lipoxygenase in nasal polyps associated with interleukin-4 promoter polymorphism -590

Abstract

OBJECTIVE:

To evaluate expression of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO) associated with interleukin (IL)-4 promoter polymorphism -590 in nasal polyp tissues.

STUDY DESIGN AND SETTING:

A prospective controlled study. A venous blood sample was taken to determine the genotype in 61 nasal polyp subjects. The C-590T variant was determined by the polymerase chain reaction-restriction fragment length polymorphism method. The expression of 5-LO and COX-2 was determined with immunohistochemical staining in 37 nasal polyp tissues associated with genotype.

RESULTS:

The genotype frequencies at position -590 of the IL-4 gene in the patients with nasal polyp were C/C (8.20%), C/T (40.98%), and T/T (50.82%). There was no significantly increased expression of COX-2 among genotypes. The 5-LO expression was significantly increased in C/C compared with C/T and T/T.

CONCLUSION:

We suggested that the IL-4 promoter polymorphism -590 C/C is associated with the expression of 5-LO in the patients with nasal polyp.

Get full access to this article

View all access options for this article.

References

Nelms

Keegan

Zamorano

, et al. The IL-4 receptor; signaling mechanisms and biologic function. Annu Rev Immunol 1999;17:701–38.

Pyo

Hur

Kim

, et al. Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and INF-7 genes in the Korean population. Hum Immunol 2003;64:979–89.

Kubo

Ransom

Webb

, et al. T-cell subset-specific expression of the IL-4 gene is regulated by a silencer element and STAT6. EMBO J 1997;16:4007–20.

Kawashima

Noguchi

Arinami

, et al. Linkage and association of an interleukin 4 gene polymorphism with atopic dermatitis in Japanese families. J Med Genet 1998;35:502–4.

Rosenwasser

Klemm

Dresback

, et al. Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 1995;2:74–8.

Yea

Yang

Park

, et al. Interleukin-4 C-590T polymorphism is associated with protection against nasal polyps in a Korean population. Am J Rhinol. In press 2006.

Charlier

Michaux

Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer nonsteroidal anti-inflammatory drugs. Eur J Med Chem 2003;38:645–59.

Pinto

Gallo

Polli

, et al. Cyclooxygenase and lipoxygenase metabolite generation in nasal polyps. Prostaglandins Leukot Essent Fatty Acids 1997;57:533–7.

Kowalski

Pawliczak

Wozniak

, et al. Differential metabolism of arachidonic acid in nasal polyp epithelial cells cultured from aspirin-sensitive and aspirin-tolerant patients. Am J Respir Crit Care Med 2000;161:391–8.

10.

Thivierge

Stankova

Rola-Pleszczynski

IL-13 and IL-4 up-regulate cysteinyl leukotriene 1 receptor expression in human monocyte and macrophages. J Immunol 2001;167:2855–60.

11.

Greisner

III Septtipane

GA.

Hereditary factor for nasal polyps. Allergy Asthma Proc 1996;17:283–6.

12.

Bidwell

Keen

Gallagher

, et al. Cytokine gene polymorphism in human disease: on-line databases, supplement 1. Genes Immun 2001;2:61–70.

13.

Smith

Garavito

DeWitt

DL.

Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 1996;271:33157–60.

14.

Niiro

Otsuka

Ogami

, et al. MAP kinase pathways as a route for regulatory mechanisms of IL-10 and IL-4 which inhibit COX-2 expression in human monocytes. Biochem Biophys Res Commun 1998; 250:200–5.

15.

Saito

Okazaki

Sugawara

, et al. Potential action of IL-4 and IL-13 as fibrogenic factors on lung fibroblasts in vitro. Int Arch Allergy Immunol 2003;132:168–76.

16.

Spaziani

Lantz

Benoit

, et al. The induction of cyclooxygenase-2(COX-2) in intact human amnion tissue by interleukin-4. Prostaglandins 1996;51:215–23.

17.

Silverman

Yandava

, et al. Pharmacogenetics of the 5-lipoxygenase pathway in asthma. Clin Exp Allergy 1998;28:164–70.

18.

Haberal

Corey

JP.

The role of leukotrienes in nasal allergy. Otolaryngol Head Neck Surg 2003;129:274–9.

19.

Zaitsu

Hamasaki

Matsuo

, et al. New induction of leukotriene A(4) hydrolase by interleukin-4 and interleukin-13 in human polymorphonuclear leukocytes. Blood 2000;96:601–9.

20.

Spanbroek

Hildner

Kohler

, et al. IL-4 determines eicosanoid formation in dendritic cells by down-regulation of 5-lipoxygenase and up-regulation of 15-lipoxygenase 1 expression. PNAS 2001;98:5152–7.