scholarly journals Interaction of Surfactant Protein A with Lipopolysaccharide and Regulation of Inflammatory Cytokines in the THP-1 Monocytic Cell Line

2000 ◽  
Vol 68 (12) ◽  
pp. 6611-6617 ◽  
Author(s):  
M. Song ◽  
D. S. Phelps
Keyword(s):  
Cell Line ◽  
Inflammatory Cytokines ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Monocytic Cell ◽  
Monocytic Cell Line

Surfactant protein A regulates cytokine production in the monocytic cell line THP-1

1997 ◽  
Vol 272 (5) ◽  
pp. L996-L1004 ◽  
Author(s):  
S. G. Kremlev ◽  
T. M. Umstead ◽  
D. S. Phelps
Keyword(s):  
Cell Line ◽  
Cytokine Production ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Tnf Alpha ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Monocytic Cell ◽  
Monocytic Cell Line

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.

Transcriptional activation and protein binding by two regions of the rat surfactant protein A promoter

1999 ◽  
Vol 277 (1) ◽  
pp. L134-L141
Author(s):  
Elizabeth Rosenberg ◽  
Feng Li ◽  
Candyce I. Smith ◽  
Samuel R. Reisher ◽  
Sheldon I. Feinstein
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Promoter Activity ◽  
Protein A ◽  
Surfactant Protein ◽  
Clara Cell ◽  
Surfactant Protein A ◽  
Type Ii ◽  
Recognition Element ◽  
Type Ii Cell

Surfactant protein A (SP-A) is expressed in lung alveolar type II cells and bronchiolar Clara cells. We have identified two active regions in the promoter of the rat SP-A gene by deletion analysis of a plasmid containing 163 bp before the start of transcription (−163 bp), linked to a reporter gene. Constructs were transfected into lung cell lines derived from each of the cell types that produces SP-A. We found a novel region of promoter activity at ∼90 bp before the transcriptional start (SP-A−90). Mutation of four nucleotides in SP-A−90 that are highly conserved among species (−92 to −89 bp) decreased expression of the SP-A construct by ∼50% in both cell lines. Electrophoretic mobility shift analysis showed specific binding to SP-A−90 by nuclear proteins from the cell lines, as well as from rat lung and liver. The electrophoretic mobility of the bands shifted by lung nuclear proteins changed late in fetal development. Although in the Clara cell line no reduction of promoter activity was seen on deletion of the region upstream of SP-A−90, in the type II cell line, deletion of residues −163 to −133 did reduce activity by ∼50%. This region contains a recognition element for thyroid transcription factor-1 (TTF-1). Endogenous TTF-1 binding activity was substantially higher in the type II cell line than in the Clara cell line, but cotransfection of a TTF-1 expression plasmid enhanced expression of the SP-A construct better in the Clara cell line than in the type II cell line. These results suggest that the recognition element for TTF-1 has varying activity in the lung cell lines of different origin due to the availability of TTF-1.

scholarly journals Jaagsiekte Sheep Retrovirus Proviral Clone JSRVJS7, Derived from the JS7 Lung Tumor Cell Line, Induces Ovine Pulmonary Carcinoma and Is Integrated into the Surfactant Protein A Gene

2001 ◽  
Vol 75 (9) ◽  
pp. 4239-4246 ◽  
Author(s):  
James C. DeMartini ◽  
Jeanette V. Bishop ◽  
Thomas E. Allen ◽  
F. A. Jassim ◽  
J. Michael Sharp ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Lung Tumor ◽  
Protein A ◽  
Tumor Cell Line ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Jaagsiekte Sheep Retrovirus ◽  
Pulmonary Carcinoma ◽  
Lung Tumor Cell

ABSTRACT Ovine pulmonary carcinoma (OPC) is a contagious neoplasm of alveolar epithelial type II (ATII) or Clara cells caused by a type D/B chimeric retrovirus, jaagsiekte sheep retrovirus (JSRV). Here we report the isolation, sequencing, pathogenicity, and integration site of a JSRV provirus isolated from a sheep lung tumor cell line (JS7). The sequence of the virus was 93 to 99% identical to other JSRV isolates and contained all of the expected open reading frames. To produce virions and test its infectivity, the JS7 provirus (JSRVJS7) was cloned into a plasmid containing a cytomegalovirus promoter and transfected into 293T cells. After intratracheal inoculation with virions from concentrated supernatant fluid, JSRV-associated OPC lesions were found in one of four lambs, confirming that JSRVJS7 is pathogenic. In JS7-cell DNA, the viral genome was inserted in the protein-coding region for the surfactant protein A (SP-A) gene, which is highly expressed in ATII cells, in an orientation opposite to the direction of transcription of the SP-A gene. No significant transcription was detected from either the viral or the SP-A gene promoter in the JS7 cell line at passage level 170. The oncogenic significance of the JSRV proviral insertion involving the SP-A locus in the JS7 tumor cell line is unknown.

Comparison of SP-A and LPS effects on the THP-1 monocytic cell line

2000 ◽  
Vol 279 (1) ◽  
pp. L110-L117 ◽  
Author(s):  
Mingchen Song ◽  
David S. Phelps
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Polymyxin B ◽  
Inhibitory Effects ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocytic Cells ◽  
Similar Treatment ◽  
Tnf Α ◽  
Factor Α

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-α (TNF-α), interleukin-1β (IL-1β), and IL-8 are reduced by >60% if SP-A is preincubated with Survanta (200 μg/ml) for 15 min before addition to THP-1 cells. However, the LPS effects on TNF-α and IL-8 are inhibited by <20% and the effect on IL-1β 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-α, IL-1β, and IL-8. Similar treatment with SP-A reduces TNF-α, but IL-1β 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.

Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line

1997 ◽  
Vol 273 (2) ◽  
pp. L382-L388 ◽  
Author(s):  
M. Koptides ◽  
T. M. Umstead ◽  
J. Floros ◽  
D. S. Phelps
Keyword(s):  
Cell Line ◽  
Cell Function ◽  
Immune Cell ◽  
Surfactant Protein ◽  
Surface Proteins ◽  
Mrna Levels ◽  
Nf Kappa B ◽  
Simultaneous Treatment ◽  
Monocytic Cell ◽  
Monocytic Cell Line

The expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor (NF)-kappa B. Because surfactant protein (SP) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-kappa B. We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line, a human monocytic cell line. Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids. Moreover, the NF-kappa B inhibitors blocked SP-A-dependent increases in tumor necrosis factor-alpha mRNA levels. These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung.

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