ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE2 Expression in A549 Cells

Role of P2 Receptor-Dependent STAT3 Activation

Shin Ei Cheng, I-Ta Lee, Chih Chung Lin, Wan Ling Wu, Li Der Hsiao, Chuen Mao Yang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: Up-regulation of cyclooxygenase (COX)-2 and its metabolite prostaglandin E2 (PGE2) are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE2 release remain unclear. Principal Findings: Here, we showed that ATPγS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin), PKC (Gö6983, Gö6976, Ro318220, and Rottlerin), ROS (Edaravone), NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin], Jak2 (AG490), and STAT3 [cucurbitacin E (CBE)] and transfection with siRNAs of PKCα, PKCι, PKCμ, p47phox, Jak2, STAT3, and cPLA2 markedly reduced ATPγS-induced COX-2 expression and PGE2 production. In addition, pretreatment with the inhibitors of P2 receptor attenuated phox translocation 2 production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA2 signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation will create opportunities for the development of anti-inflammation therapeutic strategies.

Original languageEnglish
Article numbere54125
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 17 2013
Externally publishedYes

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NADPH Oxidase
prostaglandin synthase
Cyclooxygenase 2
Dinoprostone
prostaglandins
Adenosine Triphosphate
Chemical activation
receptors
inflammation
cells
Pneumonia
pretreatment
lungs
suramin
cucurbitacins
Purinergic P2 Receptors
Suramin
Signal transduction
transfection
Metabolites

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE2 Expression in A549 Cells : Role of P2 Receptor-Dependent STAT3 Activation. / Cheng, Shin Ei; Lee, I-Ta; Lin, Chih Chung; Wu, Wan Ling; Hsiao, Li Der; Yang, Chuen Mao.

In: PLoS One, Vol. 8, No. 1, e54125, 17.01.2013.

Research output: Contribution to journalArticle

Cheng, Shin Ei ; Lee, I-Ta ; Lin, Chih Chung ; Wu, Wan Ling ; Hsiao, Li Der ; Yang, Chuen Mao. / ATP Mediates NADPH Oxidase/ROS Generation and COX-2/PGE2 Expression in A549 Cells : Role of P2 Receptor-Dependent STAT3 Activation. In: PLoS One. 2013 ; Vol. 8, No. 1.
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