Published online before print February 5, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0607412v1 83/5/1249    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reimer, T. Articles by Jungi, T. W. Search for Related Content PubMed PubMed Citation Articles by Reimer, T. Articles by Jungi, T. W.

(Journal of Leukocyte Biology. 2008;83:1249-1257.)
© 2008 by Society for Leukocyte Biology

poly(I:C) and LPS induce distinct IRF3 and NF-B signaling during type-I IFN and TNF responses in human macrophages

Institute of Veterinary Virology, University of Bern, Bern, Switzerland

¹Correspondence: Institute of Veterinary Virology, University of Bern, Laenggassstrasse 122, Bern CH-3001, Switzerland. E-mail: reimer{at}ivv.unibe.ch

Macrophages play major roles in the onset of immune responses and inflammation by inducing a variety of cytokines such as TNF and IFN-β. The pathogen-associated molecular pattern, polyinosinic-polycytidylic acid [poly(I:C)], and LPS were used to study type-I IFN and TNF responses in human macrophages. Additionally, activation of the key signaling pathways, IFN-regulatory factor 3 (IRF3) and NF-B, were studied. We found that TNF production occurred rapidly after LPS stimulation. LPS induced a strong IFN-β mRNA response within a short time-frame, which subsided at 8 h. The IFN-stimulated genes (ISGs), ISG56 and IFN-inducible protein 10, were strongly induced by LPS. These responses were associated with NF-B and IRF3 activation, as shown by IRF3 dimerization and by nuclear translocation assays. poly(I:C), on the other hand, induced a strong and long-lasting (>12 h) IFN-β mRNA and protein response, particularly when transfected, whereas only a protracted TNF response was observed when poly(I:C) was transfected. However, these responses were induced in the absence of detectable IRF3 and NF-B signaling. Thus, in human macrophages, poly(I:C) treatment induces a distinct cytokine response when compared with murine macrophages. Additionally, a robust IFN-β response can be induced in the absence of detectable IRF3 activation.

Key Words: signal transduction • interferon • transcription factors • gene regulation • cytokines • innate immunity

This article has been cited by other articles:

				R. S. Noyce, S. E. Collins, and K. L. Mossman Differential Modification of Interferon Regulatory Factor 3 following Virus Particle Entry J. Virol., May 1, 2009; 83(9): 4013 - 4022. [Abstract] [Full Text] [PDF]

				S. M. Ngoi, M. G. Tovey, and A. T. Vella Targeting Poly(I:C) to the TLR3-Independent Pathway Boosts Effector CD8 T Cell Differentiation through IFN-{alpha}/{beta} J. Immunol., December 1, 2008; 181(11): 7670 - 7680. [Abstract] [Full Text] [PDF]