The Role of PARP1 in Monocyte and Macrophage Commitment and Specification: Future Perspectives and Limitations for the Treatment of Monocyte and Macrophage Relevant Diseases with PARP Inhibitors.

摘要: Modulation of PARP1 expression, changes in its enzymatic activity, post-translational modifications, and inflammasome-dependent cleavage play an important role the development monocytes numerous subtypes highly specialized macrophages. Transcription is governed by proliferation status cells at each step their development. Higher abundance embryonic stem hematopoietic precursors supports self-renewal pluri-/multipotency, whereas a low level enzyme determines pattern surface receptors signal transducers that are functionally linked to NFκB pathway. In macrophages, involvement regulation transcription, signaling, inflammasome metabolism, redox balance macrophage polarization towards pro-inflammatory phenotype (M1), which drives host defense against pathogens. On other hand, it seems limit variety subsets anti-inflammatory myeloid effectors (M2), help remove tissue debris achieve healing. PARP inhibitors, prevent protein ADP-ribosylation, PARP1‒DNA traps, capture on chromatin, may allow us modulate immune responses particular cell types. They can be also effective treatment monocytic leukemia cancers reverting anti- proinflammatory tumor-associated