In:
Respiration, S. Karger AG, Vol. 78, No. 3 ( 2009), p. 312-321
Abstract:
〈 i 〉 Background: 〈 /i 〉 The Gly80Ser polymorphism in phospholipase A2-IID ( 〈 i 〉 PLA2G2D, 〈 /i 〉 NCBI SNP reference: rs584367) is associated with a loss in body weight in patients with chronic obstructive pulmonary disease (COPD). The T allele missense mutation results in the 80th amino acid of the 〈 i 〉 PLA2G2D 〈 /i 〉 protein changing from a glycine (Gly; C allele) to a serine (Ser; T allele). COPD patients carrying Ser lose a significant amount of weight compared with those carrying Gly. The mechanism for this weight loss following carriage of this Ser allele has not been clarified. 〈 i 〉 Objectives: 〈 /i 〉 We aimed to evaluate whether this allelic change alters PLA2 enzymatic activity and/or pro-inflammatory cytokine inducibility. 〈 i 〉 Methods: 〈 /i 〉 A549 cells (a human pulmonary epithelial cell line) were transfected with 〈 i 〉 PLA2G2D 〈 /i 〉 -Gly or 〈 i 〉 PLA2G2D 〈 /i 〉 -Ser. We evaluated PLA2 activity and cytokine expressions in these cells. 〈 i 〉 Results: 〈 /i 〉 The enzymatic activity of sPLA2 in A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Ser cells did not differ from the A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Gly cells. A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Ser cells spontaneously produced higher levels of interleukin (IL)-6 and IL-8 than A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Gly cells. Upon tumor necrosis factor-α stimulation, IL-6 and IL-8 mRNA and protein levels in A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Ser cells were elevated compared with those of A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Gly cells. Upon hydrogen peroxide stimulation, IL-8 mRNA and protein levels in A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Ser cells were higher than those of A549- 〈 i 〉 PLA2G2D 〈 /i 〉 -Gly cells. 〈 i 〉 Conclusions: 〈 /i 〉 〈 i 〉 PLA2G2D 〈 /i 〉 -Ser enhances the expression of IL-6 and IL-8 compared with 〈 i 〉 PLA2G2D 〈 /i 〉 -Gly. This enhanced cytokine expression observed with the allelic change in 〈 i 〉 PLA2G2D 〈 /i 〉 may be associated with the body weight loss seen in COPD patients.
Type of Medium:
Online Resource
ISSN:
0025-7931
,
1423-0356
Language:
English
Publisher:
S. Karger AG
Publication Date:
2009
detail.hit.zdb_id:
1464419-8
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