Fig. 7. Proposed mechanism of action of PP-007 involved in resolving lung inflammation in CF.

a During infection, circulating monocytes migrate to the lungs. Because of the defective induction of HO-1, recruited CF MΦs fail to acquire an anti-inflammatory phenotype. This leads to an enhanced nonresolving proinflammatory environment with elevated numbers of IL-17-producing cells that may contribute to lung neutrophilia. b PP-007 induces high levels of HO-1 in circulating monocytes recruited to lung tissue. Rescue of HO-1 expression primes lung monocyte-derived MΦs to acquire an anti-inflammatory profile that helps to reduce proinflammatory cytokine levels and IL-17-producing cell recruitment and to expedite the elimination of lung neutrophils.