Mutational switch of an IL-6 response to an interferon-γ-like response

Ana P. Costa-Pereira, Silvia Tininini, Birgit Strobl, Tonino Alonzi, Joerg F. Schlaak, Hayaatun Is'harc, Ida Gesualdo, Sally J. Newman, Ian M. Kerr, Valeria Poli

Research output: Contribution to journalArticle

Abstract

Signaling through Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is central to the responses to the majority of cytokines and some growth factors, including the interferons (IFNs) and the IL-6 family of cytokines. The biological responses to stimulation through the widely distributed IL-6 and IFN-γ receptors are, however, completely different. Remarkably, it is shown here that, in mouse embryo fibroblasts lacking STAT3, IL-6 mediates an IFN-γ-like response including prolonged activation of STAT1, the induction of multiple IFN-γ-inducible genes, the expression of class II MHC antigens, and an antiviral state. Normal cells exposed to IL-6 thus require a STAT3-dependent function(s) to down-regulate STAT1 activity and prevent an IFN-γ-like response. The data encourage the view that the very disparate IFN-γ and IL-6 JAK/receptor complexes mediate a common set of generic or "core" signals which are subject to STAT3-dependent modulation to provide IL-6 specificity. The switching of one cytokine response to one closely mimicking another as a result of the loss of a single signaling component has profound implications, for example, for the interpretation of the phenotypes of knockout mice and for the clinical use of inhibitors of signaling.

Original languageEnglish
Pages (from-to)8043-8047
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number12
DOIs
Publication statusPublished - Jun 11 2002

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Interferons
Interleukin-6
Janus Kinases
Cytokines
Interferon Receptors
Interleukin-6 Receptors
Histocompatibility Antigens Class II
Transducers
Knockout Mice
Antiviral Agents
Intercellular Signaling Peptides and Proteins
Down-Regulation
Embryonic Structures
Fibroblasts
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mutational switch of an IL-6 response to an interferon-γ-like response. / Costa-Pereira, Ana P.; Tininini, Silvia; Strobl, Birgit; Alonzi, Tonino; Schlaak, Joerg F.; Is'harc, Hayaatun; Gesualdo, Ida; Newman, Sally J.; Kerr, Ian M.; Poli, Valeria.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 12, 11.06.2002, p. 8043-8047.

Research output: Contribution to journalArticle

Costa-Pereira, AP, Tininini, S, Strobl, B, Alonzi, T, Schlaak, JF, Is'harc, H, Gesualdo, I, Newman, SJ, Kerr, IM & Poli, V 2002, 'Mutational switch of an IL-6 response to an interferon-γ-like response', Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 12, pp. 8043-8047. https://doi.org/10.1073/pnas.122236099
Costa-Pereira, Ana P. ; Tininini, Silvia ; Strobl, Birgit ; Alonzi, Tonino ; Schlaak, Joerg F. ; Is'harc, Hayaatun ; Gesualdo, Ida ; Newman, Sally J. ; Kerr, Ian M. ; Poli, Valeria. / Mutational switch of an IL-6 response to an interferon-γ-like response. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 12. pp. 8043-8047.
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