① Damage-associated molecular patterns (DAMPs) and IL-1α released by sterile injury or pathogen-associated molecular patterns (PAMPs) released by infectious injury to tissues activate resident macrophages through receptors involving pattern recognition receptors (PRRs). ② The activated macrophages produce pro-inflammatory cytokines such as IL-1α, IL-1β, or TNF-α to initiate the inflammatory cascade. ③ Simultaneously, the pro-inflammatory cytokines and probably other signals from injured cells activate MSCs to secrete anti-inflammatory factors that include TSG-6, PGE2, and IL-1ra that either modulate the activation of the resident macrophages or decrease the downstream effects of the pro-inflammatory cytokines. ④ The net effect is to decrease the amplification of the pro-inflammatory signals from resident macrophages by parenchymal cells through the secretion of IL-6, CXCL1, and related factors and to decrease the recruitment of neutrophils. Reprinted with permission from Macmillan Publishers Ltd (Prockop and Oh, 2011).