FANCC-deficient hematopoietic stem together with progenitor cells are sensitized to avariety of inhibitory cytokines, considered one of which, TNFα, can induce bone marrowfailure and clonal evolution in Fancc-deficient mice. FANCC-deficientmacrophages are also hypersensitive to toll-like receptor activation and produceTNFα in the unrestrained fashion. Reasoning that suppression of inhibitorycytokine production might enhance hematopoiesis, people screened small moleculesusing TLR-agonist-stimulated FANCC- and FANCA-deficient macrophagescontaining an NF-kappaB/AP-1 receptive reporter gene (SEAP). In the 75small molecules screened, this p38 MAPK inhibitor BIRB 796 together with dasatinib, potently suppressed TLR8-dependent expression with the reporter gene. FAmacrophages were hypersensitive
Leave a comment