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Lipopolysaccharide (LPS) amplifies cigarette smoke (CS)‐induced release of IL‐1 beta and TNF‐alpha from macrophages via indirectly acting on neurokinin 1 receptor (NK1R)
Author(s) -
Xu Junyang,
Xu Fadi,
Zhang Cancan,
Lin Yong
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1025.3
Subject(s) - lipopolysaccharide , chemistry , secretion , tumor necrosis factor alpha , substance p , proinflammatory cytokine , nf κb , in vitro , macrophage , receptor , tachykinin receptor 1 , pharmacology , receptor antagonist , antagonist , inflammation , signal transduction , biology , endocrinology , biochemistry , neuropeptide , immunology
CS increases secretion of IL‐1 beta and TNF‐alpha from macrophages in human, which is amplified by LPS exposure. The mechanism underlying this amplification remains unclear. CS and LPS promote macrophage release of substance P (SP) that activates macrophage NK1R to secrete these cytokines, and NF‐κB participates in NK1R intracellular signaling and synthesis of these cytokines. Thus, we asked whether LPS amplified these cytokines response to CS via increasing the macrophage release of SP that binds with NK1R to activate NF‐κB in vitro. RAW264.7 macrophages were incubated with CS condensate (CSC) and DMSO alone or coupled with LPS and/or NK1R antagonist (aprepitant). We found that compared to DMSO, the responses of supernatant IL‐1 beta, TNF‐alpha, SP and nuclear NF‐κB activation to: 1) CSC were increased by 2‐, 11‐, 0.4‐ and 1‐fold; 2) LPS by 4‐, 21‐, 0.3‐, and 2‐fold; and 3) CSC+LPS by 9‐, 50‐, 2‐, and 5‐fold. The data indicate that LPS amplifies the macrophages′ responses of cytokines as well as SP and NF‐κB to CSC. Aprepitant strikingly reduced the LPS amplificatory effects on IL‐1 beta, TNF‐alpha, and NF‐κB activation by 36%, 39%, and 58%, respectively. Our study in vitro confirms that LPS amplifies the CS‐induced secretion of these cytokines from macrophages, and further demonstrates that NK1R is responsible for this amplification, presumably via the NF‐κB pathway. (Supported by NIH 74183)