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Impaired COX‐2/PGE2‐mediated anti‐viral response in G6PDknockdown A549 cells through NOX/MAPK signaling
Author(s) -
Lin Hsin Ru,
Wu Yi Hsuan,
Yang Chuen Mao,
Chiu Daniel Tsun Yee
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb106
Subject(s) - gene knockdown , mapk/erk pathway , microbiology and biotechnology , tumor necrosis factor alpha , a549 cell , p38 mitogen activated protein kinases , inflammation , signal transduction , jurkat cells , oxidative stress , chemistry , biology , immunology , immune system , cell , t cell , apoptosis , biochemistry
Glucose‐6‐phosphate dehydrogenase (G6PD) provides reducing power to all cells in the form of NADPH to meet the cellular needs for reductive biosynthesis and maintenance of the cellular redox homeostasis. We have previously reported that G6PD‐deficient cells suffer high oxidative stress and these cells are more susceptible to viral infection than normal counterparts. However, how G6PD deficiency may affect cellular signaling remains elusive. Toward this end, we determined the effects of G6PD status on inflammatory responses with TNF‐α to stimulate cells (15 ng/ml TNF‐α). By comparing the level of TNF‐α induced inflammatory response, decreased expression pattern of induced Cox‐2 and downstream PGE2 production were observed in G6PD‐knockdown A549 cells. We further analyzed TNF‐α‐induced antiviral activity and found that decreased PGE2 production enhanced cells more susceptible to Coronavirus 229E infection. Further investigation revealed that these phenomena were due to decreased phosphorylation level of MAPK (p38, ERK and JNK) comparing with control cells. By applying DPI pretreatment, the impaired inflammatory response in G6PD‐knockdown cells was through NOX signaling. All in all, these data suggest that G6PD status affects cellular inflammatory responses and decreased TNF‐α‐mediated anti‐viral response in G6PD‐knockdown A549 cells is due to dysregulated NOX/MAPK signaling.