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Am J Physiol Lung Cell Mol Physiol 274: L289-L295, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 2, L289-L295, February 1998

Regulation of surfactant proteins A and B by TNF-alpha and phorbol ester independent of NF-kappa B

Gloria S. Pryhuber, Rubia Khalak, and Qian Zhao

Departments of Pediatrics and Environmental Medicine, Strong Children's Research Center, University of Rochester Medical Center, Rochester, New York 14642

Acute lung inflammation is complicated by altered pulmonary surfactant phospholipid and protein composition. The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha ) and the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) inhibit expression of surfactant-associated proteins A and B (SP-A and SP-B), both important for normal surfactant function. The transcription factor nuclear factor-kappa B (NF-kappa B) frequently mediates regulation of gene expression by TPA and TNF-alpha . In the present study, electrophoretic mobility shift assays (EMSAs) and pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappa B activation, were utilized to determine the role of NF-kappa B activation in TPA and TNF-alpha inhibition of the surfactant proteins in NCI-H441 cells. Pentoxifylline (PTX), which inhibits TNF-alpha cellular effects without preventing NF-kappa B activation, was also tested. By EMSA, TPA and TNF-alpha increased nuclear NF-kappa B binding activity in temporally distinct patterns. PDTC decreased TPA- and TNF-alpha -induced NF-kappa B binding activity but did not limit their inhibition of SP-A and SP-B mRNAs. PDTC independently decreased both SP-A and SP-B mRNAs. PTX partially reversed TNF-alpha - but not TPA-mediated inhibition of SP-A and SP-B mRNAs without altering NF-kappa B binding. The effects of PDTC and PTX on NF-kappa B and the surfactant proteins suggest that NF-kappa B activation does not mediate TPA or TNF-alpha inhibition of SP-A and SP-B mRNA accumulation.

tumor necrosis factor-alpha ; nuclear factor-kappa B; pyrrolidine dithiocarbamate; pentoxifylline; dexamethasone; adenocarcinoma


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