Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of neutrophil function have been highly correlated with severe, early onset periodontal diseases. Nonetheless, the identification of these patients and diagnosis of specific disease states, such as LJP or prepubertal periodontitis, are difficult and costly. In this report, the identification and quantification of neutrophil cell surface markers specific to LJP patients with neutrophil chemotaxis defects are described. GP110 and FMLP receptors were quantified by flow cytometry on neutrophils from LJP patients with neutrophil chemotaxis defects, LJP patients without chemotaxis defects, other patients with primary neutrophil chemotaxis defects, and controls. Results suggest that reduction of GP110 and FMLP receptor on neutrophils is specific for LJP patients who exhibit neutrophil chemotaxis abnormalities.
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PMID:Neutrophil surface protein markers as indicators of defective chemotaxis in LJP. 231 38

Porphyromonous gingivalis is a periodontopathic Gram-negative anaerobe associated with chronic adult periodontitis. P. gingivalis proteases are considered important virulence factors in the pathogenesis of periodontal diseases. In addition, defective bactericidal activity of neutrophils has also been observed in periodontitis. In this report we describe the effects of trypsin-like protease(s) secreted from P. gingivalis cells on the ligand binding of FMLP receptor on neutrophils. It was observed that trypsin-like protease(s) from P. gingivalis stimulate neutrophils by means of superoxide anion production. Subsequently, the proteases were found to cleave the FMLP receptor protein as evident by direct labeling of the FMLP receptor molecule. These results suggest that trypsin-like protease(s) secreted from P. gingivalis cells contribute to attenuate the bactericidal activity of neutrophils by cleaving the polypeptide chain of the FMLP receptor molecule. The finding that neutrophils after the incubation with P. gingivalis released protease preparation fail to respond to further stimulation by FMLP suggests that P. gingivalis trypsin-like protease(s) may be a possible ligand for the FMLP receptor.
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PMID:Porphyromonas gingivalis trypsin-like protease: a possible natural ligand for the neutrophil formyl peptide receptor. 814 95

Decreased neutrophil chemotaxis has been implicated in the pathophysiology of the disease, localized juvenile periodontitis (LJP). The biological basis for the altered neutrophil function in LJP has been suggested to be an intrinsic cellular defect, involving a decrease in the number of N-formyl-methionyl-leucyl-phenylalanine (FMLP) receptors on the cell surface. We have investigated the relative contribution of serum-borne factors in the modulation of neutrophil functions in LJP, in a large population of LJP patients and healthy control subjects (HS). Treatment of HS-neutrophils with LJP-sera, resulted in a decreased neutrophil chemotactic response, and down regulation of FMLP receptors on the cell surface. Pretreatment of LJP-sera with anti-TNF and anti-IL-1 antibodies effectively, although incompletely, neutralized the ability of LJP-sera to modulate chemotaxis and FMLP receptor levels in HS-neutrophils. The changes induced by LJP sera were specific and sustained and could not be reversed by placing LJP-serum treated neutrophils in HS-serum. Sera obtained from HS and patients with adult periodontitis (AP), both of which exhibit normal chemotaxis, and patients with clinically diagnosed LJP with normal neutrophil chemotaxis (LJP-nctx) did not modulate HS neutrophil chemotaxis or FMLP receptors. Furthermore, recombinant human TNF-alpha, rhIL-1 alpha and rhIL-1 beta, at very low concentrations (15 pg/ml to 150 pg/ml), modulated the chemotactic response as well as FMLP receptor numbers on HS-neutrophils, in a manner similar to those observed in LJP. The present findings demonstrate that the biologic basis for the altered neutrophil function may not be an intrinsic cellular defect in neutrophils, but at least in part due to quantitatively small but biologically significant elevations in the levels of TNF-alpha and IL-1 in the serum.
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PMID:Role of cytokines in the modulation of neutrophil chemotaxis in localized juvenile periodontitis. 815 1

The aim of this study was to evaluate neutrophil function in patients suffering from the generalized form of early onset periodontitis (EOP). We investigated neutrophil migration in vivo and neutrophil superoxide production and adhesion in response to a variety of compounds; neutrophils were isolated both from blood and a skin experimental exudate of 15 patients with EOP and of 15 sex- and age-matched normal control subjects. No difference was found in neutrophil migration in vivo (71.2+/-16.4x10(6) and 68.8+/-10.7x10(6) PMN/cm2/24 h in patients affected by early onset periodontitis and normal subjects respectively) and in adhesion. The superoxide production in response to STZ and PMA was similar between the 2 groups, while superoxide production in response to fMLP was markedly lower in patients than in control subjects both in circulating neutrophils (5.6+/-2.2 versus 10.4+/-2.3 nmoles O2-/10(6) cells, p<0.0001) and in exudate neutrophils (16.3+/-4.3 versus 22.3+/-4.7 nmoles O2-/10(6) cells, p<0.005). In general, neutrophil function in patients suffering from early onset periodontitis does not differ from control subjects, suggesting that the overall defence function of these cells is normal. The only parameter that we have found to be different between the 2 groups is the low superoxide production after fMLP stimulation. The stimulus- and function-specificity of this defect in neutrophils from patients indicates the existence of a dysregulation of the signal transduction pathway distal to fMLP receptor and proximal to NADPH oxidase activation.
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PMID:Neutrophil migration, oxidative metabolism and adhesion in early onset periodontitis. 1048 5

Polymorphonuclear neutrophils (PMNs) are attracted to sites of infection by N-formylpeptide (fMLP) chemoattractants. The high-affinity fMLP receptor (FPR1) of phagocytic cells interacts with bacterial fMLP and mediates chemotaxis, degranulation, and superoxide production. These cellular functions are disrupted in PMN from aggressive periodontitis (AP) patients. Two FPR1 gene single nucleotide polymorphisms (SNPs), c.329T>C and c.378C>G, have been associated with a localized form of AP in African-American patients. To evaluate the generality of these SNPs in AP patients, we sequenced a 363 bp interval of the FPR1 gene in an ethnically diverse group of patients (n=111) and controls (n=115). Neither c.329T>C nor c.378C>G were detected in the 452 alleles sequenced. Six SNPs were identified including two located in the FPR1 second extracellular loop that were significantly associated with the AP phenotype in African-American patients (p.R190W, P=0.0033; and p.N192K, P=0.0018). These two SNPs show three predominant haplotypes, each associated with a different disease risk in African-Americans. These data do not support the hypothesis that the FPR1 SNPs c.329T>C and c.378C>G play an etiologic role in aggressive periodontitis, but do suggest that SNPs in the second extracellular loop may be etiologically important.
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PMID:Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients. 1259 98

Formylpeptide receptor (FPR1) is involved in inflammation, which is important in the pathogenesis of diverse conditions, including common diseases and cancers. To date, little is known about the relationships between FPR1 and such diseases, aside from the fact that FPR1 is related to periodontitis, which is implicated in systemic diseases such as stomach cancer. We hypothesized that FPR1 polymorphisms related to periodontal disease may confer susceptibility to stomach cancer. Two single nucleotide polymorphisms (SNPs) in the second extracellular region and C-terminus of the formylpeptide receptor gene were analyzed in 1531 consecutive autopsy cases in the Japanese elderly. The tri-allelic SNP of rs1042229 was detected by modified melting temperature analysis. Homozygous K alleles of rs1042229 were associated with stomach cancer (Odds ratio [OR]=1.62, confidence interval [CI]=1.05-2.48, p=0.028). In the analysis of the recessive model of the K allele, FPR1 was associated with a high risk of stomach cancer (OR=1.73, CI=1.15-2.55, p=0.0075). The risk allele for stomach cancer pointed in the same direction as periodontitis. This is the first study to evaluate polymorphisms of the FPR1 gene in stomach cancer to find a positive association between these polymorphisms and stomach cancer. Further studies on the relationship between stomach cancer and the FPR1 gene are warranted.
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PMID:Polymorphisms of the formylpeptide receptor gene (FPR1) and susceptibility to stomach cancer in 1531 consecutive autopsy cases. 2121 25

Formyl peptide receptors (FPRs) expressed by mammalian myeloid cells are the important part of innate immunity. They belong to the seven-transmembrane domain class of receptors coupled to heterotrimeric GTP-binding proteins. Binding of the receptor with a wide spectrum of exogenous and endogenous ligands triggers such defensive phagocyte reactions as chemotaxis, secretory degranulation, and respiratory burst, keeping a balance of inflammatory and antiinflammatory processes in the organism. The association between single nucleotide polymorphisms in the gene of FPR1 receptor resulting in disruption of the receptor structure and the development of certain pathologies accompanied with inflammation, such as aggressive periodontitis, macular degeneration, and even gastric cancer (Maney, P., and Walters, J. D. (2009) J. Periodontol., 80, 1498-1505; Liang, X. Y., et al. (2014) Eye, 28, 1502-1510; Otani, T., et al. (2011) Biochem. Biophys. Res. Commun., 405, 356-361) has been shown. In this review, we matched the missense mutation of formyl-peptide receptors with their known functional domains and classified them according to their potential significance in pathology.
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PMID:Formyl Peptide Receptor Polymorphisms: 27 Most Possible Ways for Phagocyte Dysfunction. 2837 99

Aggressive periodontitis is a rare but rapidly progressing form of periodontal disease that usually affects otherwise systemically healthy individuals, at a young age. It usually affects first molars and incisors, which are usually lost if treatment is not properly and early rendered. Although of low prevalence, it affects individuals of African descent at a higher prevalence, and usually multiple members within the same family. Several studies have been performed in the attempt to evaluate specific single nucleotide polymorphisms (SNPs) that could be associated with this disease. To the best of our knowledge, the present article provides the first review of the literature focusing on studies that evaluated SNPs in patients of African descent with aggressive periodontitis. Several SNPs have been evaluated in different genes according to their role in the pathogenesis of the disease, with positive and negative associations (such as IL1, FCGR3B, FPR1, LTF, CYBA, GLT6D1, TLR4) with both the localized and generalized forms of aggressive periodontitis. Given the complexity of periodontitis, the difficulty in gathering large cohorts diagnosed with this rare form of disease, and the fact that candidate gene studies may only determine part of the genetic risk of a disease, the search for specific SNPs associated with aggressive periodontitis seems to be a long one, most likely to result in the combination of multiple SNPs, in multiple genes.
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PMID:Genetic polymorphisms and periodontal disease in populations of African descent: A review. 2910 64