Interaction of surfactant protein A with lipopolysaccharide and regulation of inflammatory cytokines in the THP-1 monocytic cell line.
Pulmonary surfactant protein A (SP-A) is involved in innate immunity in the lung. In this study we investigated the interaction of SP-A with different serotypes of lipopolysaccharide (LPS) on the regulation of inflammatory cytokines in vitro. In the human monocytic cell line, THP-1, combining SP-A with lipid A or rough LPS further enhanced lipid A- or rough LPS-stimulated tumor necrosis factor alpha (TNF-alpha) mRNA levels, while SP-A-elicited increases in TNF-alpha mRNA levels were partially neutralized. In contrast, the combination of smooth LPS and SP-A resulted in additive effects on TNF-alpha mRNA levels. We also demonstrated that there was cross-tolerance between SP-A and LPS in THP-1 cells. Pretreatment of THP-1 cells with LPS modestly inhibited the response of these cells to subsequent challenge with SP-A, with regard to the production of TNF-alpha, whereas there was no or little effect on the production of interleukin-1beta (IL-1beta) and IL-8. Conversely, pretreatment of THP-1 cells with SP-A markedly increased the response to subsequent challenge with LPS with regard to the production of IL-1beta and IL-8, although the production of TNF-alpha was modestly decreased. However, a synergistic stimulatory effect was observed when the two agents were added simultaneously to the cells. NF-kappaB formation was downregulated in SP-A- but not in LPS-induced tolerant cells. These results suggested that SP-A exhibits different interactions with distinct serotypes of LPS. In addition, SP-A is different from LPS with regard to the induction of cross-tolerance, and these actions may be mediated, at least in part, through different mechanisms.
Song
M
M
Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Phelps
D S
DS
D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008050:Lipid A / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011510:Proteolipids / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D008050:Lipid A; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha