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

Activity of the leukotriene pathway in Barrett’s metaplasia and oesophageal adenocarcinoma
Activity of the leukotriene pathway in Barrett’s metaplasia and oesophageal adenocarcinoma
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.
1023-3830
1379-1384
Shutt, James David
00af0d59-a00c-48e0-b4eb-c9d6de82bc24
Boger, Philip
bc7ca73e-a8ab-42be-b509-642f17981ba1
Neale, James Richard
97fea948-1718-4d47-a5e5-8ea7a3480308
Patel, Praful
c92dd012-6d09-43b2-9fac-aaadcb42ea27
Sampson, Anthony Peter
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Shutt, James David
00af0d59-a00c-48e0-b4eb-c9d6de82bc24
Boger, Philip
bc7ca73e-a8ab-42be-b509-642f17981ba1
Neale, James Richard
97fea948-1718-4d47-a5e5-8ea7a3480308
Patel, Praful
c92dd012-6d09-43b2-9fac-aaadcb42ea27
Sampson, Anthony Peter
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60

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)

Record type: Article

Abstract

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.

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e-pub ahead of print date: 1 August 2012
Published date: December 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 341313
URI: http://eprints.soton.ac.uk/id/eprint/341313
ISSN: 1023-3830
PURE UUID: 858abed6-d653-4c40-8008-d85a14621c76
ORCID for Anthony Peter Sampson: ORCID iD orcid.org/0009-0008-9653-8935

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Date deposited: 19 Jul 2012 09:23
Last modified: 15 Mar 2024 02:50

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Contributors

Author: James David Shutt
Author: Philip Boger
Author: James Richard Neale
Author: Praful Patel

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