Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha.

Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Research Abstract Details 

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Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Abstract Text:

Lisa S Berenson,Maya Gavrieli,J David Farrar,Theresa L Murphy,Kenneth M Murphy,

The role of type I IFN in Th1 development, STAT4 activation, and IFN-gamma production in murine T cells has remained unresolved despite extensive examination. Initial studies indicated that IFN-alpha induced Th1 development and IFN-gamma production in human, but not murine, T cells, suggesting species-specific differences in signaling. Later studies suggested that IFN-alpha also induced Th1 development in mice, similar to IL-12. More recent studies have questioned whether IFN-alpha actually induces Th1 development even in the human system. In the present study, we compared the capacity of IL-12 and IFN-alpha to induce Th1 differentiation, STAT4 phosphorylation, and IFN-gamma production in murine T cells. First, we show that IFN-alpha, in contrast to IL-12, cannot induce Th1 development. However, in differentiated Th1 cells, IFN-alpha can induce transient, but not sustained, STAT4 phosphorylation and, in synergy with IL-18, can induce transient, but not sustained, IFN-gamma production in Th1 cells, in contrast to the sustained actions of IL-12. Furthermore, loss of STAT1 increases IFN-alpha-induced STAT4 phosphorylation, but does not generate levels of STAT4 activation or IFN-gamma production achieved by IL-12 or convert transient STAT4 activation into a sustained response. Our findings agree with recent observations in human T cells that IFN-alpha-induced STAT4 activation is transient and unable to induce Th1 development, and indicate that IFN-alpha may act similarly in human and murine T cells.

Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Publishing Authors By Initials

LS Berenson,M Gavrieli,JD Farrar,TL Murphy,KM Murphy,

For similar cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes: cd4-positive t-lymphocytes: t-lymphocytes, helper-inducer: th1 cells research abstracts see: cells: blood cells: leukocytes: leukocytes, mononuclear: lymphocytes: t-lymphocytes: cd4-positive t-lymphocytes: t-lymphocytes, helper-inducer: th1 cells research

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Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 177

Page Numbers: 5195-203

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Oct

YEAR: 2006

Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Keywords Mesh Terms:

KEYWORDS: Th1 Cells

MESH TERMS: drug effects

Chemical & Substance for Abstract: Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha. Information

Substance Name: Interleukin-12

Registry Number: 187348-17-0

Grant and Affiliation Information for Distinct characteristics of murine STAT4 activation in response to IL-12 and IFN-alpha.

AFFILIATION: Department of Pathology and Center for Immunology, Washington University of School of Medicine, St Louis, MO 63110, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: P50 HL54619

ACRONYM: HL

MEDLINETA: J Immunol

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