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


OBJECTIVE
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.
Igarashi
Akira
A
Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, Yamagata, Japan.
Shibata
Yoko
Y
Yamauchi
Keiko
K
Osaka
Daisuke
D
Takabatake
Noriaki
N
Abe
Shuichi
S
Inoue
Sumito
S
Kimura
Tomomi
T
Yamaguchi
Yoko
Y
Ishizaki
Jun
J
Hanasaki
Kohji
K
Kubota
Isao
I
D002460:Cell Line; D004614:Emaciation / Q000201:enzymology* / Q000209:etiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D020125:Mutation, Missense; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054501:Group II Phospholipases A2