Cigarette Smoke Synergizes Lipopolysaccharide-Induced InterIeukin-1β and Tumor Necrosis Factor–α Secretion from Macrophages via Substance P–Mediated Nuclear Factor–κB Activation

A recent study has indicated that alveolar macrophages from smokers incubated with lipopolysaccharide (LPS) secrete much more IL-1β and TNF-α than those from healthy nonsmokers, but the mechanisms underlying this augmented secretion by cigarette smoke (CS) remain unknown. CS and LPS reportedly promote macrophages' secreting substance P (SP) that could up-regulate these cytokines' secretion from macrophages by acting on neurokinin 1 receptor (NK1R). Moreover, NF-κB from macrophages participates in NK1R intracellular signaling and synthesis of these cytokines. The present in vitro study was undertaken to examine whether CS is able to synergize these cytokines' response to LPS in macrophages, and if so, whether an amplified SP secretion is responsible for this synergistic cytokines' response via a NK1R-driven NF-κB pathway. THP-1–derived and MH-S macrophages were exposed to control medium and CS condensate (CSC) without or with LPS. We found that LPS, CSC, and CSC+LPS significantly increased IL-1β, TNF-α, an...