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Nociceptive Sensory Neurons (NSNs) Promote Alveolar Macrophages' (AMs) Synthesis of Matrix Metalloproteinases (MMPs) during Cigarette Smoke (CS) via Releasing Substance P (SP)
Author(s) -
Xu Junyang,
Xu Fadi
Publication year - 2010
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.24.1_supplement.31.11
Subject(s) - matrix metalloproteinase , chemistry , substance p , receptor , antagonist , in vitro , nociception , pharmacology , medicine , neuropeptide , biochemistry
CS up‐regulates AMs' MMP‐2, ‐9, and ‐12 expressions, contributing to the pathogenesis of COPD. Although SP released from NSNs' fibers in the lungs during CS is a key factor in producing pulmonary MMPs, its direct effect on AMs' synthesizing these MMPs is unknown. We asked if NSNs directly interact with AMs in promoting SP release and enhancing AMs' MMPs expression, especially during CS, in this study in vitro. AMs (MH‐S macrophages) and NSNs (50B11 neurons) were separate‐ or co‐cultured for 12 h without or with pretreatment of neurokinin 1 receptor (NK1R) antagonist (aprepitant and CP‐99,994) under control and CS condition, respectively. We found that: 1) under control, SP in supernatant and MMP‐12 rather than MMP‐2 and ‐9 in AMs were significantly higher in the co‐cultured preparation than the sum of the separate‐cultured preparations; 2) in the co‐cultured preparation, SP and MMP‐2, ‐9, and ‐12 expression were further increased by 4.5‐, 4.4‐, 8‐, and 2.4‐fold (P < 0.05), respectively, in 3 μg/ml CS‐treated preparation, compared to the control, with little change in the cells' viability; 3) MMPs were not detectable in NSNs at all conditions; and 4) NK1R antagonists strikingly reduced the CS's modulatory effects on the MMPs in the co‐cultured AMs by 30%–43%. Our results suggest an important role of SP in AMs' synthesis of MMPs induced by the interaction of NSNs and AMs, particularly during CS exposure.