Surfactant protein A regulates cytokine production in the monocytic cell line THP-1.
Surfactant lipids inhibit cytokine production by immune cells, and surfactant protein A (SP-A) stimulates it. By enzyme-linked immunosorbent assay and mRNA blotting, we studied proinflammatory cytokine production by the monocytic cell line THP-1. SP-A caused increases in tumor necrosis factor (TNF)-alpha within 1 h, peaking at 4 h and then declining. Interleukin (IL)-1 beta increased and stayed elevated for 24 h. SP-A stimulated IL-8 also, peaking at 4 h, rapidly declining, and peaking again at 24 h. SP-A-dependent changes were detected for IL-6, but at higher SP-A doses. mRNA levels for TNF-alpha and IL-1 beta increased in response to SP-A, peaking within 2 h. The increases in TNF-alpha mRNA and protein induced by SP-A were inhibited by surfactant lipids. For IL-1 beta and IL-8, the lipids either had no inhibitory influence or inhibited less than for TNF-alpha. This suggests that the ability of macrophages to participate in inflammatory reactions is enhanced by SP-A alone or by mixtures of lipids and SP-A containing more SP-A than in normal surfactant, as occurs in many conditions leading to inflammation.
Kremlev
S G
SG
Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Umstead
T M
TM
Phelps
D S
DS
D001688:Biological Products; D002454:Cell Differentiation; D004338:Drug Combinations; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001688:Biological Products; D004338:Drug Combinations; D007375:Interleukin-1; D016209:Interleukin-8; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; C072197:beractant