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Surfactant Phospholipids Suppress the Inflammation of Bronchial Epithelium Induced by TLR2 and TLR3 Ligands

¹ Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Dennis R. Voelker, Ph.D., Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: voelkerd{at}njc.org

Pulmonary surfactant is a lipid and protein complex that functions to reduce the surface tension of the alveolar compartment and prevent collapse at end-expiration. Recently, we determined that a minor component of pulmonary surfactant phopholipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG), could markedly attenuate the inflammatory response (production of TNF- and nitric oxide) induced by lipopolysaccharide (LPS) in human and rodent macrophages. The POPG acts by disrupting CD14 binding to LPS, and MD2 binding to Toll-like receptor (TLR)4. POPG can also inhibit the inflammatory response of macrophages induced by agonists of TLR2 (Pam3Cys), and TLR3 (dsRNA; Poly IC). The aim of this study was to determine the function of surfactant lipids, especially POPG, regulating the innate immune response of bronchial epithelium. We stimulated the bronchial epithelial cell line, Beas2B, and normal human bronchial epithelial cells (NHBE) with the TLR2 agonist, Pam3Cys, and the TLR3 agonist, poly IC, and measured the secretion of IL-6 and IL-8. POPG acted as a potent inhibitor of cytokine production, induced by Pam3 Cys and dsRNA. Control studies revealed that POPG was not toxic to bronchial epithelial cells and did not affect cell viability. These results demonstrated that POPG can act on the epithelium in addition to macrophages to suppress the inflammatory response elicited by ligation and activation of multiple TLRs. These findings raise the possibility that supplementation of the injured lung with POPG may suppress inflammation and hasten repair processes.

FOOTNOTES

Supported by NIH HL 073907 (D.R.V.).

Conflict of Interest Statement: M.N. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.W.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. E.D.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.R.V. and National Jewish Medical and Research Center have filed a patent for using unsaturated anionic lipids as TLR antagonists.

(Received in original form August 8, 2007; accepted in final form October 16, 2007)

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nakamura, M. Articles by Voelker, D. R. PubMed Articles by Nakamura, M. Articles by Voelker, D. R.