Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein

Tumor necrosis factor-α (TNFα) decreased the expression of pulmonary surfactant proteins SP-A and SP-B in human pulmonary adenocarcinoma cell lines. The effect of TNFα on SP-A content and mRNA in the pulmonary adenocarcinoma cell line, H441-4, was concentration and time dependent. TNFα decreased the cellular content of SP-A to < 10% of control 48 h after addition. TNFα decreased de novo synthesis of SP-A and decreased the accumulation of SP-A in media. SP-A mRNA was decreased within 12 h of addition of TNFα, with nearly complete loss of SP-A mRNA observed after 24 h. Inhibitory effects of TNFα on SP-A mRNA were dose-related with nearly complete inhibition of SP-A mRNA caused by 25 ng/ml TNFα. The effects of TNFα on SP-A were distinct from the effects of Interferon γ which increased SP-A content approximately twofold in H441-4 cells. TNFγ also decreased the content of SP-B mRNA. In contrast to the inhibitory effect of TNFγ on SP-A and SP-B mRNA, TNFγ increased mRNA encoding human manganese superoxide dismutase (Mn-SOD). TNFγ did not inhibit growth, alter cell viability or β-actin mRNA in either cell line. These in vitro studies demonstrate the marked pretranslational inhibitory effects of the cytokine, TNFβ, on the expression of pulmonary surfactant proteins, SP-A and SP-B. The results support the concept that macrophage-derived cytokines may control surfactant protein expression.