Clinical association between chronic periodontitis and the leukocyte extravasation inhibitors developmental endothelial locus‐1 and pentraxin‐3

Abstract

This clinical study aimed to determine whether periodontal disease is associated with expression of developmental endothelial locus-1 (Del-1) and pentraxin-3 (PTX-3), endogenous inhibitors of leukocyte extravasation in humans. Expression of DEL1, PTX3, interleukin-17A (IL17A), and lymphocyte function-associated antigen-1 (LFA1) was determined, using RT-PCR and melting curve analysis, in biopsies of gingival tissues from 95 patients: 42 with moderate periodontitis; 40 with severe periodontitis; and 13 healthy controls. Relative expression of DEL1 and PTX3 was statistically significantly weaker in patients with periodontitis than in the control subjects. On the contrary, both IL17A and LFA1 showed statistically significant stronger expression in patients with periodontitis than in healthy controls. Correlation analysis, performed using Spearman's test, showed that expression of DEL1 was statistically significantly linked to periodontitis (ρ = -0.103) and to age (ρ = -0.134), but not to the gender of the patient, and that expression of PTX3 was significantly correlated with periodontitis (ρ = -0.354). Expression of neutrophil extravasation inhibitors DEL1 and PTX3 show significant, but weak, association with the clinical manifestation of chronic periodontitis.

DHEA Inhibits Leukocyte Recruitment through Regulation of the Integrin Antagonist DEL-1

“…*p , 0.05. thereby, leukocyte recruitment (8,9). Reduced DEL-1 expression is observed in several inflammatory conditions, such as human and murine periodontitis, multiple sclerosis, and its murine counterpart, experimental autoimmune encephalomyelitis (EAE), inflammation-related adrenal gland dysfunction, and in human and murine inflammatory lung pathologies (7,14,15,(17)(18)(19)63). Whereas reduced DEL-1 expression leading to increased inflammatory cell recruitment may be beneficial in acute infections, decreased DEL-1 levels in a chronic setting may exacerbate inflammatory pathologic conditions as seen in naturally occurring periodontitis in mice (9).…”

“…Interestingly, high expression of DEL-1 is observed in immunoprivileged organs, such as the brain, which also exhibit relatively high concentrations of NGF and DHEA (8,19,29,(75)(76)(77). Intriguingly, aging in humans is associated with increased circulating levels of TNF and decreased levels of DHEA, although an age-related decline of DEL-1 expression is described in mice and humans as well (9,26,63,78). It is thus tempting to speculate that the inverse associations between inflammatory cytokines, such as TNF, and the anti-inflammatory factors DHEA and DEL-1 in the context of inflammatory diseases and aging may be mechanistically linked and may represent an "inflamm-aging" signature.…”

Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients

“…The genes encoding important molecules involved in periodontal inflammation identified in previously published articles include matrix metallopeptidases including MMP1 , MMP2 , MMP3 , MMP8 , MMP9 and MMP13 and tissue inhibitors of metalloproteinases including TIMP1 , TIMP3 and TIMP4 ; various interleukin (IL) families including IL1 β, IL2 , IL4 , IL6 , IL8 , IL10 , IL11 , IL 12 , IL17A , IL17F , IL18 , IL21 , IL23 and IL35 ; the pentraxin family including C‐reactive protein/pentraxin 1 ( CRP / PTX1 ) and pentraxin 3 ( PTX3 ); the TNF superfamily TNF‐ α and the receptor activator of the NFκB ligand/TNF superfamily member 11 ( RANKL / TNFSF11 ); the TNF receptor superfamily osteoprotegerin/TNF receptor superfamily member 11b ( OPG / TNFRSF11B ); the transforming growth factor (TGF) superfamily TGF β 1 ; the TLR family including TLR2 and TLR4 ; chemokines including C‐C motif chemokine ligands ( CCL2 , CCL3 , CCL5 , CCL19 , CCL20 ), C‐C motif chemokine receptor 4 ( CCR4 ) and C‐X‐C motif chemokine ligands ( CXCL6 , CXCL8 / IL8 ); suppressors of cytokine signalling including SOCS1 and SOCS3 ; interferon IFN‐ γ; transcription regulator T‐box 21 ( TBX21 ); NF κ B / NFKB1 ; TNF‐α‐induced protein 3 ( TNFAIP3 ); peptidylprolyl isomerase A/cyclophilin A ( PPIA / CypA ); and cyclooxygenase 2/prostaglandin‐endoperoxide synthase 2 ( COX2/PTGS2 ) . By combining the retrieval and computer algorithm prediction results, potential target genes related to periodontal inflammation were determined.…”

“…Genes were regarded as putative targets when they were identified in at least three of four databases. Four databases were used for target identification: miRDB 4.0 (http://www.mirdb.org/), IL1β, IL2, IL4, IL6, IL8, IL10, IL11, IL 12, IL17A, IL17F, IL18, IL21, IL23 and IL35; [19][20][21][22][23][24][25][26][27] the pentraxin family including Creactive protein/pentraxin 1 (CRP/PTX1) and pentraxin 3 (PTX3) 28,29 ;…”

New developments in neutrophil biology and periodontitis

“…Intriguingly, developmental endothelial locus‐1 mRNA and protein expression in gingival tissue are progressively diminished with aging, correlating with excessive neutrophil recruitment and interleukin‐17‐dependent inflammatory bone loss in old wild‐type mice . The aging‐related decline in developmental endothelial locus‐1 expression in the gingiva was recently confirmed in humans by an independent group . Replenishment of developmental endothelial locus‐1 in old mice via local injection of recombinant developmental endothelial locus‐1 expressed as an Fc fusion protein (Del‐1‐Fc) inhibits interleukin‐17 production, LFA‐1‐dependent neutrophil infiltration, and bone loss .…”