Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

David F. Stroncek, Christopher Basil, Dirk Nagorsen, Sara Deola, Eleonora Aricó, Kina Smith, Ena Wang, Francesco M. Marincola, Monica C. Panelli

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Interferon (IFN)-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS) stimulation in vitro. Results: Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-α1, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their subclassification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. Conclusion: Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in autoimmunity and tumor rejection by including and/or excluding an array of related factors likely to be heterogeneously expressed by distinct sub-populations of individuals in sickness or in response to biological therapy.

Original languageEnglish
Article number24
JournalJournal of Translational Medicine
Volume3
DOIs
Publication statusPublished - 13 Jun 2005
Externally publishedYes

Fingerprint

Interferon Type I
Phagocytes
Interferons
Protein Isoforms
Polarization
Cytokines
Lipopolysaccharides
Chemical activation
Biological Therapy
Interleukins
Gene Expression Profiling
Hepatitis C
Orthomyxoviridae
Autoimmunity
Chemokines
Gene expression
Modulators
Interferon-gamma
Tumors
Amino Acid Sequence

Keywords

  • Autoimmunity
  • Interferon
  • Macrophages

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms. / Stroncek, David F.; Basil, Christopher; Nagorsen, Dirk; Deola, Sara; Aricó, Eleonora; Smith, Kina; Wang, Ena; Marincola, Francesco M.; Panelli, Monica C.

In: Journal of Translational Medicine, Vol. 3, 24, 13.06.2005.

Research output: Contribution to journalArticle

Stroncek, David F. ; Basil, Christopher ; Nagorsen, Dirk ; Deola, Sara ; Aricó, Eleonora ; Smith, Kina ; Wang, Ena ; Marincola, Francesco M. ; Panelli, Monica C. / Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms. In: Journal of Translational Medicine. 2005 ; Vol. 3.
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