Differential gene expression in neutrophils from patients with generalized aggressive periodontitis

Abstract

Differential gene expression was investigated in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). The cells were isolated from 3 groups of subjects: patients with generalized aggressive periodontitis (Aggressive-P. n = 6), generalized chronic periodontitis (Chronic-P, n = 6) and healthy controls (H, n = 8). Our results show that 37 genes were upregulated. while 27 genes were down-regulated in all Aggressive-P neutrophils by using RAP-PCR with 45 primer pairs. Reverse transcription-PCR analyses revealed that mRNA levels were significantly different (p<0.05) for heat shock transcription factor 4b (HSF4b) gene. Kruppel-like zinc finger transcription factor 9 (Zf9) and muskelin genes. HSF4b was greater in neutrophils from Aggressive-P compared to groups H and Chronic-P. Zf9 and muskelin genes were lower in Aggressive-P compared to the H groups, but no significant difference was noted compared to the Chronic-P group. The control genes, IL-1beta and VEGF genes, were expressed at a significantly higher level in Aggressive-P and Chronic-P than H (p<.01, p<0.05). In conclusion, the RAP-PCR technique used in this study enabled us to identify 3 Aggressive-P related genes, which had not been reported previously. Neutrophil functions in Aggressive-P patients are suggested to be altered by regulatory factors of the immune system including HSF4b (transcription factor), Zf9 (activator of TGF-beta) and muskelin (cellular adhesion).

Immunoexpression of Angiogenesis, Nitric Oxide Synthase, and Proliferation Markers in Gingival Samples of Patients With Aggressive and Chronic Periodontitis

“…Interestingly, other studies 7,38 contradicted Bullon et al's findings 3 and, therefore, support the results of the present study, which shows that VEGF is an important factor in the initiation and progression of gingivitis to periodontitis, with the supportive expansion of the vascular network that is concurrent with progression of the inflammation. Furthermore, in agreement with the present study, Kubota et al 4 demonstrated significantly higher levels of interleukin‐1β and VEGF messenger RNA in aggressive periodontitis neutrophils when compared to CP and healthy control neutrophils.…”

“…Previous studies 3,4,34 demonstrated quantitative and qualitative changes in the vasculature of the periodontal connective tissues. Chapple et al 34 reported a disturbed regulation in the angiogenesis subjacent to the periodontal pocket epithelium, which manifested an altered expression of VEGF.…”

“…The concept that specific microorganisms act as etiologic agents of periodontal disease that results in clinical attachment loss and alveolar bone loss is well established and accepted 1 . Currently, there are two classified forms of periodontitis: chronic periodontitis (CP) and aggressive periodontitis; 2 for the latter type, very few studies have been reported, especially if angiogenesis‐related 3,4 . Angiogenesis is a process of vascular induction that has a relevant role in wound healing, inflammatory diseases, and tumors 5 .…”

Periodontitis Associates with a Type 1 IFN Signature in Peripheral Blood Neutrophils

“…These transcriptional changes may indicate an enhanced capacity for protein synthesis and/or other functions these molecules mediate in periodontitis (43). Interestingly, members of this same group of genes were also upregulated in neutrophils primed with GM-CSF (12), a growth factor known to be associated with neutrophil-mediated pathology (44,45) and recently implicated in production of heightened baseline levels of extracellular ROS by neutrophils in chronic periodontitis (9).…”

Intra- and interindividual variation in gene expression in human adipose tissue

“…COPEB is expressed in pre-adipocytes [26] and is one of the many immediate early genes following adipogenic stimulation. However, it is also expressed in large number of other cell types such as endothelial cells [33], neurophils [36] and fibroblasts [64], allowing for differences in expression due to differences in sample constitution. We conclude that adipose samples within one depot are highly homogenous and that analysis of one biopsy will provide representative data for a single depot.…”