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Cigarette smoke (cs) or degeneration of pulmonary C‐fibers (PCFs) in mice changes alveolar macrophages’ (AM's) NK1Rs and MMP‐12 responses to substance P (SP) in vitro
Author(s) -
Xu Junyang,
Xu Fadi
Publication year - 2008
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.22.1_supplement.710.8
Subject(s) - matrix metalloproteinase , downregulation and upregulation , in vitro , chemistry , andrology , pathology , lung , capsaicin , degeneration (medical) , microbiology and biotechnology , medicine , biology , biochemistry , gene , receptor
SP binds with AMs’ NK1Rs to increase MMP‐12, a key contributor to emphysema development in mice. Since SP is released from PCFs during CS, we asked whether pulmonary SP and AMs’ NK1Rs and MMP‐12 expression were affected by CS exposure or PCF degeneration, and these treatments altered the responses of AMs’ NK1Rs and MMP‐12 to SP in vitro. Female C3H/HeN mice were exposed to filtered air (FA) or CS for 16 weeks (Series I), or received vehicle or neonatal capsaicin treatment (NCT) to produce PCF degeneration (Series II). AMs and lungs were collected after euthanasia. SP and mRNA of NK1R and MMP‐12 were detected using enzyme immunoassay and real‐time PCR, respectively. CS significantly increased pulmonary SP by 31% associated with an elevation of NK1Rs and MMP‐12 in the lungs (89% and 247%) and AMs (119% and 294%), while NCT decreased pulmonary SP by 75% associated with reduction of NK1Rs and MMP‐12 in the lungs (64% and 48%) and AMs (65% and 55%). AMs from these mice were subsequently cultured with control medium and SP (10 −8 M) for 24 h. SP profoundly upregulated AMs’ NK1Rs and MMP‐12 expression that were 76% and 52% higher in the AMs obtained from CS‐ than FA‐exposed mice. Surprisingly, these SP regulatory effects were almost eliminated after PCF degeneration. Our results suggest a CS‐ and PCF degeneration‐induced AMs’ plasticity in SP‐induced upregulation of NK1Rs and MMP‐12 expression (Supported by NIH 74183).