| First Author | Wang D | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 9 | Pages | 5757-62 |
| PubMed ID | 19380823 | Mgi Jnum | J:147705 |
| Mgi Id | MGI:3842003 | Doi | 10.4049/jimmunol.0803861 |
| Citation | Wang D, et al. (2009) NF-kappaB p50 regulates C/EBPalpha expression and inflammatory cytokine-induced neutrophil production. J Immunol 182(9):5757-62 |
| abstractText | NF-kappaB is a key transcriptional inducer of the inflammatory response in mature myeloid cells, and also stimulates cell survival, but its role in immature myeloid cell development has not been well characterized. C/EBPalpha is required for the development of monocytic and granulocytic myeloid cells from early progenitors, and NF-kappaB and C/EBPbeta cooperatively induce several inflammatory mediators. Having found that C/EBPalpha binds NF-kappaB p50 preferentially compared with NF-kappaB p65, we have now investigated myelopoiesis in nfkb1(-/-) mice lacking NF-kappaB p50. Absence of p50 leads to a significant reduction in the number of granulocytic progenitors, CFU-granulocyte, obtained with G-CSF or GM-CSF in vitro and reduces neutrophil production in vivo in response to G-CSF, with preservation of monopoiesis in vitro in response to cytokines or LPS. To gain insight into the mechanism underlying reduced granulopoiesis in the absence of NF-kappaB p50, we assessed the expression of several myeloid regulatory proteins in lineage-negative, immature myeloid cells. Although PU.1, C/EBPbeta, and STAT3 levels were unchanged, C/EBPalpha protein and RNA levels were reduced approximately 3-fold in the absence of NF-kappaB p50. In addition, NF-kappaB p50 and C/EBPalpha bound the endogenous C/EBPalpha promoter in a chromatin immunoprecipitation assay, and NF-kappaB p50 trans activated the C/EBPalpha promoter, alone or in cooperation with C/EBPalpha. Despite reduction of C/EBPalpha, G-CSFR and M-CSFR levels were maintained in total marrow and in lineage-negative cells. Together, these data indicate that acute inflammation not only activates mature myeloid cells, but also stimulates neutrophil production via NF-kappaB p50 induction of C/EBPalpha transcription. |
