Strong and persistent microbial and inflammatory stimuli overcome the genetic predisposition to higher matrix metalloproteinase-1 (MMP-1) expression: a mechanistic explanation for the lack of association of MMP1-1607 single-nucleotide polymorphism genotypes with MMP-1 expression in chronic periodontitis lesions.
OBJECTIVE
Our objective was to evaluate the association between the MMP1-1607 single-nucleotide polymorphism (SNP), periodontopathogens and inflammatory cytokines with matrix metalloproteinase-1 (MMP-1) mRNA levels in vitro and in vivo.


METHODS
This study investigated the influence of genetic (MMP1-1607 SNP), microbial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Actinobacillus actinomycetemcomitans) and inflammatory [tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)] factors on the determination of MMP-1 mRNA levels in periodontal tissues of non-smoker chronic periodontitis (CP, N=178) and control (C, N=190) groups. The effects of single and repeated lipopolysaccharide (LPS) and inflammatory cytokine stimulation of macrophages with distinct MMP1-1607 SNP genotypes were also investigated.


RESULTS
In healthy tissues, the MMP1-1607 2G allele was associated with higher MMP-1 levels while in CP MMP-1 levels were associated with the presence and load of periodontopathogens, and also with TNF-alpha and IL-1beta expression irrespective of the MMP1-1607 genotype. In vitro data demonstrate that in 2G macrophages low- and intermediate-dose LPS and TNF-alpha+IL-1beta stimulation was associated with increased MMP-1 expression, while strong and repeated stimulation resulted in higher MMP-1 levels irrespective of the MMP1-1607 genotype.


CONCLUSIONS
Our data demonstrate a limited role for MMP1-1607 SNP in periodontitis, where the extensive chronic antigenic challenge exposure overcomes the genetic control and plays a major role in the determination of MMP-1 expression.
Repeke
Carlos Eduardo
CE
Department of Biological Sciences, School of Dentistry of Bauru, São Paulo University - FOB/USP, Bauru, SP, Brazil.
Trombone
Ana Paula Favaro
AP
Ferreira
Samuel B
SB
Cardoso
Cristina R
CR
Silveira
Elcia Maria
EM
Martins
Walter
W
Trevilatto
Paula Cristina
PC
Silva
João Santana
JS
Campanelli
Ana Paula
AP
Garlet
Gustavo Pompermaier
GP
D000328:Adult; D000942:Antigens, Bacterial / Q000502:physiology; D001421:Bacteria, Anaerobic / Q000235:genetics / Q000502:physiology*; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000201:enzymology* / Q000235:genetics / Q000382:microbiology*; D016207:Cytokines / Q000378:metabolism*; D004269:DNA, Bacterial / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000502:physiology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000942:Antigens, Bacterial; D016207:Cytokines; D004269:DNA, Bacterial; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1