Comparison of SP-A and LPS effects on the THP-1 monocytic cell line.
Surfactant protein A (SP-A) increases production of proinflammatory cytokines by monocytic cells, including THP-1 cells, as does lipopolysaccharide (LPS). Herein we report differences in responses to these agents. First, polymyxin B inhibits the LPS response but not the SP-A response. Second, SP-A-induced increases in tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-8 are reduced by >60% if SP-A is preincubated with Survanta (200 microgram/ml) for 15 min before addition to THP-1 cells. However, the LPS effects on TNF-alpha and IL-8 are inhibited by <20% and the effect on IL-1beta by <50%. Third, at Survanta levels of 1 mg/ml, SP-A-induced responses are reduced by >90%, and although the inhibitory effects on LPS action increase, they still do not reach those seen with SP-A. Finally, we tested whether SP-A could induce tolerance as LPS does. Pretreatment of THP-1 cells with LPS inhibits their response to subsequent LPS treatment 24 h later, including TNF-alpha, IL-1beta, and IL-8. Similar treatment with SP-A reduces TNF-alpha, but IL-1beta and IL-8 are further increased by the second treatment with SP-A rather than inhibited as with LPS. Thus, whereas both SP-A and LPS stimulate cytokine production, their mechanisms differ with respect to inhibition by surfactant lipids and in ability to induce tolerance.
Song
M
M
Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Phelps
D S
DS
D001688:Biological Products; D002460:Cell Line; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology*; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D001688:Biological Products; D016207:Cytokines; D008070:Lipopolysaccharides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B; C072197:beractant