1. Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis.
- Author
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Kreisel, Daniel, Sugimoto, Seiichiro, Tietjens, Jeremy, Jihong Zhu, Yamamoto, Sumiharu, Krupnick, Alexander S., Carmody, Ruaidhri J., Gelman, Andrew E., and Zhu, Jihong
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GRANULOCYTES , *TISSUE wounds , *PELVIC inflammatory disease , *LEUKEMIA , *LYMPHOMAS , *LUNG injuries - Abstract
Granulocytes are pivotal regulators of tissue injury. However, the transcriptional mechanisms that regulate granulopoiesis under inflammatory conditions are poorly understood. Here we show that the transcriptional coregulator B cell leukemia/lymphoma 3 (Bcl3) limits granulopoiesis under emergency (i.e., inflammatory) conditions, but not homeostatic conditions. Treatment of mouse myeloid progenitors with G-CSF--serum concentrations of which rise under inflammatory conditions--rapidly increased Bcl3 transcript accumulation in a STAT3-dependent manner. Bcl3-deficient myeloid progenitors demonstrated an enhanced capacity to proliferate and differentiate into granulocytes following G-CSF stimulation, whereas the accumulation of Bcl3 protein attenuated granulopoiesis in an NF-κB p50-dependent manner. In a clinically relevant model of transplant-mediated lung ischemia reperfusion injury, expression of Bcl3 in recipients inhibited emergency granulopoiesis and limited acute graft damage. These data demonstrate a critical role for Bcl3 in regulating emergency granulopoiesis and suggest that targeting the differentiation of myeloid progenitors may be a therapeutic strategy for preventing inflammatory lung injury. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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