A pathway involving protein kinase Cδ up-regulates cytosolic phospholipase A 2α in airway epithelium

Hye Jin You, Jee Won Lee, Yung Joon Yoo, Jae Hong Kim

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Cytosolic phospholipase A 2α (cPLA 2α) catalyzes the hydrolysis of glycerophospholipids at the sn-2 position to liberate fatty acids. Although cPLA 2α has been implicated in various cellular processes, the detailed mechanism of its expression remains to be elucidated. Here we report that phorbol 12-myristate 13-acetate (PMA) up-regulates cPLA 2α in A549 airway epithelium cells, and that this effect is sensitive to rottlerin, a potent inhibitor of protein kinase Cδ (PKCδ). Consistent with this observation, a dominant negative mutant of PKCδ reduced cPLA 2α induction in response to PMA. Up-regulation of cPLA 2α by PMA was also inhibited by PDTC, an inhibitor of nuclear factor-kappa B (NF-κB), and degradation of IκB and subsequent activation of NF-κB occurred in response to PMA treatment. These findings indicate that PMA induces expression of cPLA 2α at the transcriptional level via an NF-κB-dependent mechanism. In addition, activation of the NF-κB promoter by PMA was diminished by pretreatment with DPI, a flavoenzyme inhibitor as well as by rottlerin, suggesting a role for reactive oxygen species (ROS) as well as PKCδ. Consistent with this, PMA stimulated the production of ROS and this was blocked by inhibiting PKCδ. Our results suggest that PKCδ and ROS lie upstream of NF-κB, and we conclude that a PKCδ-ROS-NF- κB cascade plays a pivotal role in cPLA 2α induction by PMA.

Original languageEnglish
Pages (from-to)657-664
Number of pages8
JournalBiochemical and biophysical research communications
Issue number3
Publication statusPublished - 2004 Aug 27

Bibliographical note

Funding Information:
We thank Dr. Kuroki (Institute of Molecular Oncology, Showa University, Japan) for kindly providing the adenovirus containing PKCδ DN mutant, and Dr. S.J. Lee (Korea Institute of Radiological and Medical Sciences, Seoul, Korea) for the retrovirus containing Rac1 N17 . This work was supported by grants from SRC program (Aging and Apoptosis Research Center) (2002) from the Korea Science and Engineering Foundation (KOSEF), a Molecular and Cellular BioDiscovery Research Program Grant (M10311000003-03B4500-00100), and a Frontier 21 Programs (proteomics; to J.H. Kim) from the Ministry of Science and Technology, South Korea.


  • NF-κB
  • PKCδ
  • PMA
  • ROS
  • cPLA α

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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