Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases

TY - JOUR

T1 - Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signaling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases

AU - Zhou, Zhangle

AU - Hamming, Ole J

AU - Ank, Nina

AU - Paludan, Søren R

AU - Nielsen, Anders L

AU - Hartmann, Rune

AU - Nielsen, Anders Lade

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Type III interferon (IFN) is a novel member of the interferon family. Type III IFN utilizes a receptor complex different from that of type I IFN, but both types of IFN induce STAT1, STAT2, and STAT3 activation. Here we describe a detailed comparison of signal transduction initiated by type I and type III IFN. Gene expression array analysis showed that IFN types I and III induced a similar subset of genes. In particular, no genes were induced uniquely by type III IFN. Next, we used chromatin immunoprecipitation (ChIP) analysis to investigate the promoter activation by types I and III IFN. The ChIP assays demonstrated that stimulation of cells with both type I and type III IFN resulted in the recruitment of ISGF3 transcription factor components to the promoter region of responsive genes and in an increase of polymerase II loading and histone acetylation. Whereas IFN type I signaling was observed for a broad spectrum of cell lines, type III IFN signaling was more restricted. The lack of IFN type III signaling was correlated with a low expression of the IL28Ra component of the IFN type III receptor, and IL28Ra overexpression was sufficient to restore IFN type III signaling. We also tested the activation of mitogen-activated protein (MAP) kinases by type III IFN and found that type III IFN relies strongly upon both p38 and JNK MAP kinases for gene induction.

AB - Type III interferon (IFN) is a novel member of the interferon family. Type III IFN utilizes a receptor complex different from that of type I IFN, but both types of IFN induce STAT1, STAT2, and STAT3 activation. Here we describe a detailed comparison of signal transduction initiated by type I and type III IFN. Gene expression array analysis showed that IFN types I and III induced a similar subset of genes. In particular, no genes were induced uniquely by type III IFN. Next, we used chromatin immunoprecipitation (ChIP) analysis to investigate the promoter activation by types I and III IFN. The ChIP assays demonstrated that stimulation of cells with both type I and type III IFN resulted in the recruitment of ISGF3 transcription factor components to the promoter region of responsive genes and in an increase of polymerase II loading and histone acetylation. Whereas IFN type I signaling was observed for a broad spectrum of cell lines, type III IFN signaling was more restricted. The lack of IFN type III signaling was correlated with a low expression of the IL28Ra component of the IFN type III receptor, and IL28Ra overexpression was sufficient to restore IFN type III signaling. We also tested the activation of mitogen-activated protein (MAP) kinases by type III IFN and found that type III IFN relies strongly upon both p38 and JNK MAP kinases for gene induction.

KW - Cell Line

KW - Chromatin Immunoprecipitation

KW - Humans

KW - Interferons

KW - Janus Kinases

KW - Mitogen-Activated Protein Kinases

KW - STAT Transcription Factors

KW - Signal Transduction

U2 - 10.1128/JVI.02438-06

DO - 10.1128/JVI.02438-06

M3 - Journal article

C2 - 17507495

SN - 0022-538X

VL - 81

SP - 7749

EP - 7758

JO - Journal of Virology

JF - Journal of Virology

IS - 14

ER -