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Free keywords:
IFN-γ; CD14; LPS sensitization
Abstract:
Propionibacterium acnes-primed mice develop an IFN-γ- dependent hypersensitivity towards LPS. Since CD14 plays a key role in LPS-induced cell activation the regulation and function of CD14 in this sensitization process were studied in IFN-γR-/- and the respective wild-type (wt) mice. In unprimed mice, CD14 (mRNA and protein) was either absent (liver) or only weakly expressed in organs (spleen, lung) and in plasma. Priming with P.acnes led to a moderate, mainly IFN-γ-dependent up-regulation of CD14. LPS challenge of unprimed mice induced an IFN-γ-independent increase in CD14 mRNA and CD14 protein. LPS challenge of P. acnes-primed mice induced a strong CD14 overexpression. This response was completely absent in IFN-γR-/- mice and is therefore strictly IFN-γ-dependent. The requirement for CD14 in LIPS hyper- responsiveness was assessed by comparing CD14-/- and the respective wt mice with respect to their ability to produce TNF and IFN-γ, two recognized indices of LPS activity. LPS challenge without priming led to a weaker cytokine reaction in CD14-/- than in wt mice. However, priming with P.acnes enhanced the cytokine response to LPS in both wt and CD14-/- mice, although in the latter absolute levels of cytokines were lower. Therefore, hyperreactivity to LPS is characterized by an up-regulation of CD14, but the sensitization by P.acnes is not CD14 dependent.
