scholarly journals Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice

2008 ◽  
Vol 295 (1) ◽  
pp. L162-L170 ◽  
Author(s):  
J. Xu ◽  
F. Xu ◽  
E. Barrett

Metalloelastase (MMP-12), mainly produced by macrophages, has been shown to play a key role in the pathogenesis of emphysema in animal models. Chronic cigarette smoke increases pulmonary MMP-12, which is closely correlated with an elevation of pulmonary substance P (SP). Because alveolar macrophages (AMs) contain the neurokinin-1 receptor (NK1R), we tested whether SP was able to trigger the upregulation of MMP-12 synthesis in AMs by acting on the NK1R. AMs isolated from bronchoalveolar lavage cells in C3H/HeN mice were cultured with control medium or SP that was coupled without or with NK1R antagonists (CP-99,994 or aprepitant) for 24 h. We found that SP significantly increased the mRNA of MMP-12 and NK1R by 11-fold and 82%, respectively, in AMs ( P < 0.05), and these responses were abolished by NK1R antagonists with little change in the cells' viability. Because pulmonary SP is primarily released by bronchopulmonary C-fibers (PCFs), we further asked whether destruction of PCFs would reduce SP and MMP-12. Two groups of mice were pretreated with vehicle and neonatal capsaicin (NCAP) to degenerate PCFs, respectively. Our results show that NCAP treatment significantly decreased mRNA and protein levels of SP associated with a reduction NK1R and MMP-12 in the lungs and AMs. These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs.

2000 ◽  
Vol 130 (3) ◽  
pp. 505-512 ◽  
Author(s):  
Eileen F Grady ◽  
Shandra K Yoshimi ◽  
John Maa ◽  
Dahlia Valeroso ◽  
Robert K Vartanian ◽  
...  

2013 ◽  
Vol 19 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Lynnae Schwartz ◽  
Sergei V. Spitsin ◽  
John Meshki ◽  
Florin Tuluc ◽  
Steven D. Douglas ◽  
...  

Synapse ◽  
1999 ◽  
Vol 33 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Elvira Galarraga ◽  
Salvador Hern�ndez-L�pez ◽  
Dagoberto Tapia ◽  
Arturo Reyes ◽  
Jos� Bargas

2017 ◽  
Vol 13 ◽  
pp. 174480691772765 ◽  
Author(s):  
Michael J Iadarola ◽  
Matthew R Sapio ◽  
Xunde Wang ◽  
Hector Carrero ◽  
Maria Luisa Virata-Theimer ◽  
...  

2002 ◽  
Vol 10 (4) ◽  
pp. 232-246 ◽  
Author(s):  
Giorgio Santoni ◽  
Consuelo Amantini ◽  
Roberta Lucciarini ◽  
Pierluigi Pompei ◽  
Marina Perfumi ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Riffat Mehboob ◽  
Syed Amir Gilani ◽  
Amber Hassan ◽  
Sadaf ◽  
Imrana Tanvir ◽  
...  

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as “+3,” was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as “+2” (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining “+1” was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.


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