Articles |

Regulation of Phospholipase A2 by Interleulin-1 in Human Airway Smooth Muscle* FREE TO VIEW

Rudolfo M. Pascual, MD; Bharat K. Awsare, MD; Stephen A. Farber, PhD; Reynold A. Panettieri, Jr, MD; Stephen P. Peters, MD, FCCP; Raymond B. Penn, PhD
Author and Funding Information

*From the Department of Medicine, Jefferson Medical College, and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.

Correspondence to: Rodolfo M. Pascual, MD, Thomas Jefferson University, Division of Critical Care, Pulmonary Medicine, Alleergic and Immunologic Diseases, Suite 805 College Bldg, 1025 Walnut St, Philadelphia, PA 19107; e-mail: Rodolfo.Pascual@mail.tju.edu

Chest. 2003;123(3_suppl):433S-434S. doi:10.1378/chest.123.3_suppl.433S
Text Size: A A A
Published online

Treatment of human airway smooth muscle (HASM) with interleukin (IL)-1β alone or in combination with serum or growth factors is known to induce cyclooxygenase (COX)-2 and prostaglandin E2 synthesis, an effect presumably underlying IL-1β–mediated β2 adrenergic receptor and epoprostanoid receptor desensitization and inhibition of mitogen-stimulated cell growth in HASM. Although COX-2 induction is clearly required and COX-2 activity is believed to be limiting in IL-1β-stimulated prostaglandin E2 synthesis, the role of phospholipase A2 (PLA2) in this process in unclear. We therefore assessed potential alterations in the following: (1) cytosolic PLA2 (cPLA2) protein levels, (2) cPLA2 phosphorylation state, and (3) PLA2 activity in growth-arrested HASM cultures treated with IL-1β or growth factors. Treatment with IL-1β induced a time-dependent increase in cPLA2 protein levels (assessed by immunoblotting) with a twofold increase observed at 18 h. Epidermal growth factor had only a minimal effect on cPLA2 induction, but cotreatment with IL-1β plus endothelial growth factor was synergistic, resulting in a greater than fourfold induction. cPLA2 induction was partially inhibited by the p38 inhibitor SB203580 and the classical protein kinase C inhibitor Bis I. IL-1β induced a rapid phosphorylation of cPLA2, which peaked at approximately 1 h and then waned toward basal levels by 18 h. Lastly, PLA2 activity in cultured HASM, characterized by cleavage of a phospholipid analog conjugated to a BODIPY fluorophore (D3803; Molecular Probes; Eugene, OR), was regulated by IL-1β but occurred against a background of high basal PLA2 activity in cell culture medium, suggesting an important role for secretory PLA2 in HASM arachidonate metabolism. These data suggest that regulation of HASM PLA2 activity may be important in cytokine- and growth factor-mediated eicosanoid synthesis and associated functional consequences.

Abbreviations: COX = cyclooxygenase; cPLA2 = cytosolic phospholipase A2; HASM = human airway smooth muscle; IL = interleukin; PLA2 = phospholipase A2

Dr. Pascual is recipient of a Parker B. Francis Fellowship.

This work was supported by grants HL-58506 and HL-67663.




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543