論文

査読有り 本文へのリンクあり
2001年

Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture

Infection and Immunity
  • S. Yang
  • ,
  • R. Tamai
  • ,
  • S. Akashi
  • ,
  • O. Takeuchi
  • ,
  • S. Akira
  • ,
  • S. Sugawara
  • ,
  • H. Takada

69
4
開始ページ
2045
終了ページ
2053
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1128/IAI.69.4.2045-2053.2001
出版者・発行元
AMER SOC MICROBIOLOGY

An analog of 1α,25-dihydroxyvitamin D3, 22-oxyacalcitriol (OCT), differentiated human monocytic THP-1 and U937 cells to express membrane CD14 and rendered the cells responsive to bacterial cell surface components. Both THP-1 and U937 cells expressed Toll-like receptor 4 (TLR4) on the cell surface and TLR4 mRNA in the cells, irrespective of OCT treatment. In contrast, OCT-treated U937 cells scarcely expressed TLR2 mRNA, while OCT-treated THP-1 cells expressed this transcript. Muramyldipeptide (MDP) by itself exhibited only a weak ability to induce secretion of inflammatory cytokines such as interleukin-8 (IL-8) in the OCT-differentiated THP-1 cells but showed marked synergistic effects with Salmonella lipopolysaccharide (LPS) or lipoteichoic acid (LTA) from Staphylococcus aureus, both of which exhibited strong activities. Combinatory stimulation with LPS plus LTA did not show a synergistic effect on OCT-differentiated THP-1 cells. Similar results were observed in OCT-differentiated U937 cells, although combination experiments were carried out only with MDP plus LPS. Anti-CD14 monoclonal antibody (MAb) MY4, anti-TLR4 MAb HTA125, and the synthetic lipid A precursor LA-14-PP almost completely inhibited the IL-8-inducing activities of LTA as well as LPS on OCT-treated THP-1 cells, but these treatments increased MDP activity. OCT-treated THP-1 cells primed with MDP exhibited enhanced production of IL-8 upon stimulation with LPS, while the cells primed with LPS showed no change in production upon stimulation with MDP. MDP up-regulated mRNA expression of an adapter molecule to TLRs, MyD88, to an extent similar to that for LPS in OCT-treated THP-1 cells. These findings suggested that LTA as well as LPS activated human monocytic cells in a CD14- and TLR4-dependent manner, whereas MDP exhibited activity in a CD14-, TLR4-, and probably TLR2-independent manner and exhibited synergistic and priming effects on the cells for cytokine production in response to various bacterial components.

リンク情報
DOI
https://doi.org/10.1128/IAI.69.4.2045-2053.2001
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/11254557
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000167616500010&DestApp=WOS_CPL
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0035078190&origin=inward 本文へのリンクあり
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=0035078190&origin=inward
ID情報
  • DOI : 10.1128/IAI.69.4.2045-2053.2001
  • ISSN : 0019-9567
  • PubMed ID : 11254557
  • SCOPUS ID : 0035078190
  • Web of Science ID : WOS:000167616500010

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