| First Author | Honma K | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 44 | Pages | 16001-6 |
| PubMed ID | 16243976 | Mgi Jnum | J:102927 |
| Mgi Id | MGI:3608240 | Doi | 10.1073/pnas.0504226102 |
| Citation | Honma K, et al. (2005) Interferon regulatory factor 4 negatively regulates the production of proinflammatory cytokines by macrophages in response to LPS. Proc Natl Acad Sci U S A 102(44):16001-6 |
| abstractText | A member of the IFN regulatory factor (IRF) family of transcription factors, IRF-4 is expressed in lymphocytes and macrophage/dendritic cells. Studies using IRF-4-deficient mice have revealed the critical roles of IRF-4 in lymphocyte responses. However, the role of IRF-4 in innate immune responses is not clearly understood. Here, we demonstrate that IRF-4 negatively regulates the production of proinflammatory cytokines by macrophages in response to Toll-like receptor (TLR) stimulation. Mice lacking IRF-4 are sensitive to LPS-induced shock, and their macrophages produce high levels of proinflammatory cytokines, including TNF-alpha and IL-6, in response to TLR ligands. The inhibitory role of IRF-4 in response to TLR stimulation was confirmed by the down-regulation of IRF-4 expression in normal macrophages by using the small interfering RNA technique and by the overexpression of IRF-4 in macrophage line RAW264.7. Activation of the important signaling pathways for cytokine production, NF-kappaB and JNK (c-Jun N-terminal kinase), was enhanced after LPS stimulation in IRF-4(-/-) macrophages. These results imply that IRF-4 negatively regulates TLR signaling and is inhibitory to the production of proinflammatory cytokines in response to TLR stimulation. |
