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Gly80Ser polymorphism of phospholipase A2-IID is associated with cytokine inducibility in A549 cells.

Respiration. 2009;78(3):312-21. Epub 2009 Apr 10
Akira Igarashi 1 , Yoko Shibata , Keiko Yamauchi , Daisuke Osaka , Noriaki Takabatake , Shuichi Abe , Sumito Inoue , Tomomi Kimura , Yoko Yamaguchi , Jun Ishizaki , Kohji Hanasaki , Isao Kubota
Akira Igarashi 1 , Yoko Shibata , Keiko Yamauchi , Daisuke Osaka , Noriaki Takabatake , Shuichi Abe , Sumito Inoue , Tomomi Kimura , Yoko Yamaguchi , Jun Ishizaki , Kohji Hanasaki , Isao Kubota
+ et al

[No authors listed]

Author information
  • 1 Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.

摘要


BACKGROUND:The Gly80Ser polymorphism in phospholipase A2-IID (PLA2G2D, 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 PLA2G2D 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. OBJECTIVES:We aimed to evaluate whether this allelic change alters PLA2 enzymatic activity and/or pro-inflammatory cytokine inducibility. METHODS:A549 cells (a human pulmonary epithelial cell line) were transfected with PLA2G2D-Gly or PLA2G2D-Ser. We evaluated PLA2 activity and cytokine expressions in these cells. RESULTS:The enzymatic activity of sPLA2 in A549-PLA2G2D-Ser cells did not differ from the A549-PLA2G2D-Gly cells. A549-PLA2G2D-Ser cells spontaneously produced higher levels of interleukin (IL)-6 and IL-8 than A549-PLA2G2D-Gly cells. Upon tumor necrosis factor-alpha stimulation, IL-6 and IL-8 mRNA and protein levels in A549-PLA2G2D-Ser cells were elevated compared with those of A549-PLA2G2D-Gly cells. Upon hydrogen peroxide stimulation, IL-8 mRNA and protein levels in A549-PLA2G2D-Ser cells were higher than those of A549-PLA2G2D-Gly cells. CONCLUSIONS:PLA2G2D-Ser enhances the expression of IL-6 and IL-8 compared with PLA2G2D-Gly. This enhanced cytokine expression observed with the allelic change in PLA2G2D may be associated with the body weight loss seen in COPD patients.