TY - JOUR
T1 - Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-γ
T2 - A molecular basis for priming and synergism with bacterial lipopolysaccharide
AU - Bosisio, Daniela
AU - Polentarutti, Nadia
AU - Sironi, Marina
AU - Bernasconi, Sergio
AU - Miyake, Kensuke
AU - Webb, Ginette R.
AU - Martin, Michael U.
AU - Mantovani, Alberto
AU - Muzio, Marta
PY - 2002/5/1
Y1 - 2002/5/1
N2 - In human monocytes and macrophages, interferon-γ (IFNγ) augmented mRNA and surface expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Expression of the accessory component MD-2 and of the adapter protein MyD88 was also increased. LPS increased TLR4 mRNA levels, but concomitantly decreased its surface expression. IFNγ counteracted the LPS-induced downregulation of TLR4. IFNγ-primed monocytes showed increased responsiveness to LPS in terms of phosphorylation of the interleukin-1 receptor-associated kinase (IRAK; immediately downstream of the MyD88 adapter protein), NF-κB DNA binding activity, and, accordingly, of cytokine (tumor necrosis factor α [TNFα] and interleukin-12 [IL-12]) production. These results suggest that enhanced TLR4 expression underlies the long-known priming by IFNγ of mononuclear phagocytes for pathogen recognition and killing as well as its synergism with LPS in macrophage activation.
AB - In human monocytes and macrophages, interferon-γ (IFNγ) augmented mRNA and surface expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Expression of the accessory component MD-2 and of the adapter protein MyD88 was also increased. LPS increased TLR4 mRNA levels, but concomitantly decreased its surface expression. IFNγ counteracted the LPS-induced downregulation of TLR4. IFNγ-primed monocytes showed increased responsiveness to LPS in terms of phosphorylation of the interleukin-1 receptor-associated kinase (IRAK; immediately downstream of the MyD88 adapter protein), NF-κB DNA binding activity, and, accordingly, of cytokine (tumor necrosis factor α [TNFα] and interleukin-12 [IL-12]) production. These results suggest that enhanced TLR4 expression underlies the long-known priming by IFNγ of mononuclear phagocytes for pathogen recognition and killing as well as its synergism with LPS in macrophage activation.
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U2 - 10.1182/blood.V99.9.3427
DO - 10.1182/blood.V99.9.3427
M3 - Article
C2 - 11964313
AN - SCOPUS:0036565888
VL - 99
SP - 3427
EP - 3431
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -