Activity of the leukotriene pathway in Barrett’s metaplasia and oesophageal adenocarcinoma

Shutt, James David, Boger, Philip, Neale, James Richard, Patel, Praful and Sampson, Anthony Peter (2012) Activity of the leukotriene pathway in Barrett’s metaplasia and oesophageal adenocarcinoma. Inflammation Research, 61, (12), 1379-1384. (doi:10.1007/s00011-012-0539-2). (PMID:22851204).


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OBJECTIVE: Leukotriene (LT) B(4) is a lipid inflammatory mediator implicated in tumorigenesis in animal models of Barrett's oesophagitis, but little is known about the cysteinyl-leukotrienes (LTC(4), LTD(4), LTE(4)), which have distinct inflammatory and tumorigenic actions in other tissues. We recently showed that the terminal enzymes for the synthesis of both LT families are highly expressed in human oesophageal adenocarcinoma (OA) tissues. This study therefore examined the capacity of Barrett's metaplasia (BM) and OA tissues to synthesise LTs in vitro.

SUBJECTS AND METHODS: Oesophageal biopsies from patients with BM (n = 14), high-grade dysplasia (n = 2), OA (n = 11), and squamous control tissues (n = 11) were cultured with calcium ionophore A32187 (2 ?M) for 60 min. LTB(4) and cysteinyl-leukotrienes were extracted and measured by specific enzyme immunoassays.

RESULTS: Levels of LTB(4) and cysteinyl-leukotrienes were 8.6-fold (P < 0.01) and 2.4-fold (P < 0.02) higher, respectively, in OA tissues than in squamous control tissues, but levels in BM tissues (n = 14) were not altered. Production of the two LT families correlated across all tissue types (r = 0.62, p < 0.00005).

CONCLUSIONS: Increased synthesis of LTB(4) and cysteinyl-leukotrienes has not previously been shown in human OA tissue and our results may indicate a role of these lipids in Barrett's disease progression.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1007/s00011-012-0539-2
ISSNs: 1023-3830 (print)
1420-908X (electronic)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RB Pathology
Divisions : Faculty of Medicine > Clinical and Experimental Sciences
ePrint ID: 341313
Accepted Date and Publication Date:
December 2012Published
1 August 2012Made publicly available
Date Deposited: 19 Jul 2012 09:23
Last Modified: 31 Mar 2016 14:31

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