Figure 4. Envisaged mechanism triggered by rP21 in inflammation.

rP21 induces recruitment of leukocytes to the site of inflammation and up-regulates the expression of IL-4. IL-4 is produced by lymphocytes, basophils and mastocytes and promotes a Th2 immune response. Also, IL-4 induces macrophages to acquire an Arginase-1(+) phenotype and to increase production of sFlt-1 that culminates in the inhibition of angiogenesis. Moreover, IL-4 promotes survival and differentiation of B-lymphocytes in memory cells negatively impacting on immunoglobulin production and secretion. Mastocytes in the inflammatory foci will liberate several bioactive molecules that may participate in tissue damage, recruitment of neutrophils and amplification of IL-4-driven pathways.