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Induction of CD14 expression in Lpsn, Lpsd and tumor necrosis factor receptor-deficient mice
T Takakuwa1, H P Knopf, A Sing
1Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Abstract:
The involvement of CD14 in lipopolysaccharide (LPS) recognition and signaling has been demonstrated in several studies. For this reason, we investigated whether the resistance of Lpsd mice to LPS might be related to an impaired CD14 expression. We compared the in vivo and in vitro expression of CD14 in Lpsn (LPS sensitive) and Lpsd mice, and its modulation by LPS, killed gram-negative and gram-positive bacteria and double-stranded (ds)RNA. Untreated Lpsn and Lpsd cultured macrophages (M phi), expressed similar amounts of CD14 mRNA and membrane-bound (m)CD14. LPS enhanced CD14 expression only in Lpsn M phi, while all bacteria, or dsRNA, enhanced CD14 in Lpsn and Lpsd M phi. Similarly, in vivo administration of LPS induced or enhanced CD14 mRNA in different organs of Lpsn mice only, while bacteria or dsRNA in both types of mouse. Furthermore, exogenous recombinant tumor necrosis factor (TNF) induced in vivo and in vitro enhanced CD14 expression in Lpsn, Lpsd and also in TNF receptor 2-deficient (TNFR2-/-) mice, but failed to do so in TNFR1-/- mice, showing that TNFR1 mediates the effect of TNF on CD14. However, LPS, bacteria and dsRNA induced CD14 in both TNFR2-/- and TNFR1-/- mice to a similar extent, revealing that this induction does not require TNF signaling.
Insights
CD14 expression is crucial for lipopolysaccharide (LPS) response. While LPS only enhances CD14 in sensitive mice, bacteria and dsRNA stimulate CD14 in both sensitive and resistant mice, independent of TNF signaling.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD14 is a key receptor for lipopolysaccharide (LPS) recognition and signaling.
- Previous studies indicate CD14's involvement in LPS response pathways.
- The role of CD14 in LPS-resistant (Lpsd) mice requires further investigation.
Purpose of the Study:
- To investigate CD14 expression in LPS-sensitive (Lpsn) and Lpsd mice.
- To determine the modulation of CD14 expression by LPS, bacteria, and double-stranded RNA (dsRNA).
- To elucidate the role of tumor necrosis factor (TNF) signaling in CD14 regulation.
Main Methods:
- Comparison of in vivo and in vitro CD14 expression in Lpsn and Lpsd mice.
- Treatment of cultured macrophages (M phi) with LPS, killed gram-negative and gram-positive bacteria, and dsRNA.
- Administration of LPS, bacteria, dsRNA, and recombinant TNF to mice, including TNFR1-/- and TNFR2-/- models.
Main Results:
- Macrophages from both Lpsn and Lpsd mice expressed similar baseline levels of CD14 mRNA and membrane-bound CD14 (mCD14).
- LPS enhanced CD14 expression only in Lpsn macrophages, whereas bacteria and dsRNA enhanced CD14 in both Lpsn and Lpsd macrophages.
- In vivo, LPS induced CD14 mRNA in Lpsn mice, but bacteria and dsRNA induced it in both Lpsn and Lpsd mice.
- TNF induced CD14 expression via TNFR1, but LPS, bacteria, and dsRNA induced CD14 independently of TNF signaling.
Conclusions:
- LPS resistance in Lpsd mice is not due to impaired CD14 expression.
- CD14 expression can be modulated by various microbial components and nucleic acids.
- TNF receptor 1 (TNFR1) mediates TNF-induced CD14 upregulation, but other pathways exist for microbial-induced CD14 expression.