Profile of Metalloproteinases and Their Association with Inflammatory Markers in Pleural Effusions.
Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes.



To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers.



The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant.



One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-β1showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-β1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6.



MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil. lisetepneumo@yahoo.com.br.
Lisete Ribeiro
LR
Teixeira
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.
Murilo B
MB
Dias
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.
Roberta K B
RK
Sales
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.|Clinical Laboratory and LIM 03-Department of Pathology, Hospital das Clínicas, University of Sao Paulo Medical School, São Paulo, Brazil.
Leila
L
Antonangelo
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.
Vanessa A
VA
Alvarenga
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.
Juliana
J
Puka
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.|Medical College of Jundiai, São Paulo, Brazil.
Evaldo
E
Marchi
Pleura Laboratory-Pulmonary Division, Heart Institute (InCor), University of Sao Paulo Medical School, Rua Dr. Eneas de Carvalho Aguiar, 44, Cerqueira César, São Paulo, 05403-000, Brazil.
Milena Marques Pagliarelli
MM
Acencio
D000243:Adenosine Deaminase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005122:Exudates and Transudates / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils; D016066:Pleural Effusion, Malignant / Q000201:enzymology* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000201:enzymology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D015850:Interleukin-6; C508960:TGFB1 protein, human; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D007770:L-Lactate Dehydrogenase; D045726:Metalloproteases; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C548482:ADA protein, human; D000243:Adenosine Deaminase
Cancer; Matrix metalloproteinases; Pleural effusion; Tuberculosis
Eur Respir J. 2005 Jan;25(1):104-9
15640330
Oncol Rep. 2001 Mar-Apr;8(2):421-4
11182067
Semin Respir Infect. 1999 Mar;14(1):9-17
10197393
Trends Immunol. 2001 Oct;22(10):571-9
11574282
Am J Respir Crit Care Med. 1997 Dec;156(6):1987-92
9412584
Crit Rev Oral Biol Med. 1993;4(2):197-250
8435466
Eur Respir J. 2009 Jan;33(1):134-41
18715875
Chest. 1995 Jun;107(6):1641-7
7781360
Thorax. 1993 Jul;48(7):765-9
8153928
Am J Respir Cell Mol Biol. 1992 Aug;7(2):120-5
1497900
Respirology. 2007 Sep;12(5):660-3
17875052
Chest. 1992 Dec;102(6):1808-14
1446493
J Immunol. 2001 Mar 15;166(6):4223-30
11238675
J Immunol. 1993 Dec 15;151(12):7216-23
8258721
Thromb Haemost. 2001 Jul;86(1):324-33
11487021
Eur Respir J. 1994 Nov;7(11):2062-72
7533104
FASEB J. 1991 May;5(8):2145-54
1850705
Am J Respir Cell Mol Biol. 1999 Mar;20(3):458-64
10030844
Wound Repair Regen. 1999 Nov-Dec;7(6):477-85
10633007
Interact Cardiovasc Thorac Surg. 2013 Mar;16(3):263-9
23190621
Eur Respir J. 1995 Aug;8(8):1352-6
7489803
Am J Respir Cell Mol Biol. 1996 Jun;14(6):508-15
8652179
Pharmacol Rev. 2004 Dec;56(4):549-80
15602010
Eur J Cell Biol. 1997 Oct;74(2):111-22
9352216
Am J Respir Crit Care Med. 1995 Aug;152(2):765-74
7633740
Eur Respir J. 2005 Apr;25(4):600-4
15802331
Ann Intern Med. 1972 Oct;77(4):507-13
4642731
Br J Cancer. 1999 Mar;79(9-10):1347-55
10188875
Hum Immunol. 2012 Oct;73(10):985-91
22820625
Clin Exp Immunol. 2003 Oct;134(1):138-42
12974766
Infect Immun. 2001 Sep;69(9):5661-70
11500442
Clin Infect Dis. 2000 Jul;31(1):80-4
10913401
J Immunol. 1996 Nov 1;157(9):4159-65
8892653
Cancer Res. 2001 Mar 15;61(6):2365-70
11289097
Interact Cardiovasc Thorac Surg. 2011 Mar;12(3):420-4
21172937