| First Author | Sheikh F | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 96 |
| Issue | 4 | Pages | 591-600 |
| PubMed ID | 25024400 | Mgi Jnum | J:220134 |
| Mgi Id | MGI:5632271 | Doi | 10.1189/jlb.2A0414-191R |
| Citation | Sheikh F, et al. (2014) An essential role for IFN-beta in the induction of IFN-stimulated gene expression by LPS in macrophages. J Leukoc Biol 96(4):591-600 |
| abstractText | TLR agonists such as LPS and poly(I:C) induce expression of type I IFNs, such as IFN-alpha and -beta, by macrophages. To examine the role of IFN-beta in the induction of ISGs by LPS, we compared the ability of LPS to induce ISGF3 activity and ISG expression in bone marrow-derived macrophages from WT and Ifnb1(-/-) mice. We found that LPS treatment activated ISGF3 and induced expression of ISGs such as Oas1, Mx1, Ddx58 (RIG-I), and Ifih1 (MDA5) in WT macrophages, but not in macrophages derived from Ifnb1(-/-) mice or Ifnar1(-/-) mice. The inability of LPS to induce activation of ISGF3 and ISG expression in Ifnb1(-/-) macrophages correlated with the failure of LPS to induce activation of STAT1 and -2 in these cells. Consistent with these findings, LPS treatment also failed to induce ISG expression in bone marrow-derived macrophages from Stat2 KO mice. Although activation of ISGF3 and induction of ISG expression by LPS was abrogated in Ifnb1(-/-) and Ifnar1(-/-) macrophages, activation of NF-kappaB and induction of NF-kappaB-responsive genes, such as Tnf (TNF-alpha) and Il1b (IL-1beta), were not affected by deletion of either the IFN-beta or IFN-alphaR1 genes. These findings demonstrate that induction of ISGF3 activity and ISG expression by LPS is critically dependent on intermediate production of IFN-beta and autocrine signaling through type I IFN receptors. |
