| Autor: |
Grahnert, Anja, Weiss, Ronald, Schilling, Erik, Stanslowsky, Nancy, Sack, Ulrich, Hauschildt, Sunna |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Druh dokumentu: |
Článek |
| ISSN: |
1662-811X |
| Popis: |
In response to GM-CSF or M-CSF, macrophages (MΦ) can acquire pro- or anti-inflammatory properties, respectively. Given the importance of CD14 and Toll-like receptor (TLR) 4 in lipopolysaccharide (LPS)-induced signaling, we studied the effect of anti-CD14 antibody mediated CD14 blockade on LPS-induced cytokine production, signal transduction and on the expression levels of CD14 and TLR4 in GM-MΦ and M-MΦ. We found M-MΦ to express higher levels of both surface antigens and to produce more interferon (IFN)-β and interleukin-10, but less tumor necrosis factor (TNF)-α than GM-MΦ. Blockage of CD14 at high LPS concentrations increased the production of proinflammatory cytokines and decreased that of IFN-β in M-MΦ but not in GM-MΦ. We show that phosphorylation states of signaling molecules of the MyD88 (myeloid differentiation primary response 88), TRIF (TIR-domain-containing adapter-inducing IFN-β) and MAPK (mitogen-activated protein kinase) pathways are not altered in any way that would account for the cytokine overshoot reaction. However, CD14 blockage in M-MΦ decreased TLR4 and CD14 expression levels, regardless of the presence of LPS, indicating that the loss of the surface molecules prevented LPS from initiating TRIF signaling. As TNF-α synthesis was even upregulated under these experimental conditions, we suggest that TRIF is normally involved in restricting LPSinduced TNF-α overproduction. Thus, surface CD14 plays a decisive role in the biological response by determining LPSinduced signaling. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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