The Papillon-Lefèvre and Haim Munk syndromes are characterized by the presence of both palmoplantar hyperkeratosis (PPK) and severe early onset periodontitis. It is the early onset periodontal disease component that distinguishes these from other more common forms of PPK. It has been proposed that the periodontal disease component may be a casual association in individuals with PPK. Genetic syndromes with palmoplantar keratosis and severe ealry onset periodontitis may be due to specific bacterial infections in individuals with PPK. Recently, keratin gene mutations have been identified in several conditions typified by palmoplantar keratosis. The present study sought to test the hypothesis that a keratin gene defect similar to those previously identified in other PPK conditions is responsible for the Haim Munk and the Papillon. Lefèvre syndromes. We have performed genetic linkage studies to test for linkage between polymorphic DNA loci within 2 cytokeratin gene families and the disease phenotype in Haim Munk syndrome and Papillon-Lefèvre syndrome. Families with individuals segregating for the Haim Munk syndrome and the Papillon-Lefèvre syndrome were examined to determine disease status, and genotyped for microsatellite DNA markers closely linked to the acidic (type I) and the basic (type II) cytokeratin genes on chromosomes 12 and 17. Genotype data were evaluated for microsatellite allele homozygosity in affected individuals. Results of these preliminary genetic studies suggest that the gene defect in Haim Munk syndrome is not due to a gene defect in either the type I or the type II keratin gene clusters. These findings suggest that Haim Munk syndrome may be genetically distinct from other more common forms of PPK that have been linked to the cytokeratin gene families, and suggest that mutations in genes other than keratin genes are responsible. Additional family studies are needed to confirm these preliminary findings.

An accumulation of elevated numbers of macrophages (Mø) and Ig producing cells is associated with localized and chronically inflamed gingiva of patients with adult periodontitis. When gingival lymphocytes were isolated from inflamed tissues and examined by flow cytometry, approximately 20–30% of lymphocytes were CD4+ T cells. For the analysis of Thl and Th2 cytokine expression by these CD4+ T cells, RNA was extracted and reverse transcriptase polymerase chain reaction (RT‐PCR) was performed by using specific 5′ and 3′primers for IFN‐γ and IL‐2 (Thl), IL‐4, IL‐5, IL‐6, IL‐10 and IL‐13 (Th2) and β‐actin (housekeeping gene). Two distinct cytokine profiles were noted based on the expression of selected Thl and Th2 cytokines. Thus, one pattern was represented by the expression of mRNA for IFN‐γ, IL‐6. IL‐10 and IL‐13. while the other case consisted of mRNA for IFN‐γ, IL‐6 and IL‐13. Except for a few cases, messages for IL‐2, IL‐4 and IL‐5 were not detected by cytokinespecific RT‐PCR. The predominant expression of Th2 cytokines (e.g. IL‐6. IL‐10 and IL‐13) may contribute to the induction of high B cell responses in local disease sites. On the other hand, lack of IL‐4 may be responsible for the accumulation of Mφ in diseased periodontium. We also investigated whether a relationship exists between IL‐4 receptor (IL‐4R) expression and Mø persistence in the absence of exogenous IL‐4. Gingival Mγ, when compared with monocytes (MN)/Mø from peripheral blood mononuclear cells (PBMC), expressed high levels of IL‐4R mRNA. When gingival Mø were incubated with recombinant IL‐4 (rIL‐4). the cell viability was dramatically reduced by apoptosis. These findings clearly show that the lack of IL‐4 may contribute to the persistant occurrence of Mø at the disease site and addition of exogenous rIL‐4 to gingival Mø cultures leads to cell death by apoptosis.

Periodontology 2000Volume 14, Issue 1 p. 54-78 The acute inflammatory response and the role of phagocytic cells in periodontal health and disease DAVID K. DENNISON, DAVID K. DENNISONSearch for more papers by this authorTHOMAS E. VAN DYKE, THOMAS E. VAN DYKESearch for more papers by this author DAVID K. DENNISON, DAVID K. DENNISONSearch for more papers by this authorTHOMAS E. VAN DYKE, THOMAS E. VAN DYKESearch for more papers by this author First published: 23 February 2007 https://doi.org/10.1111/j.1600-0757.1997.tb00192.xCitations: 105AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. 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THIS POSITION PAPER WAS PREPARED BY THE Research, Science and Therapy Committee of The American Academy of Periodontology and is intended for the information of the dental profession. The purpose of the paper is to provide the reader with a general overview of the relationship of tobacco use and periodontal diseases. This paper will review the epidemiological and clinical findings that have led to our understanding of the role of tobacco use in relation to periodontal diseases and their treatment. In addition, this paper will review the possible underlying mechanisms for these effects from tobacco use. The practitioner can use this information in treatment decisions and in giving advice to the patients who use tobacco products.

Lipopolysaccharide is one of the most potent trigger substances for monocytes and macrophages causing secretion of inflammatory mediators such as tumor necrosis factor and interleukin-1. The nature of the nuclear factors involved in regulation of these cytokine genes is still unknown. Nuclear factor kappa B (NF-kappa B; heterodimer of p50 and p65) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with lipopolysaccharide. Nonsteroidal anti-inflammatory drugs such as salicylates have been used to treat symptoms of inflammation, and a new mechanism of drug action was suggested recently. Salicylates have been shown to inhibit lipopolysaccharide-induced gene transcription via inhibition of NF-kappa B activation by preventing the degradation of NF-kappa B inhibitor "I kappa B", blocking the translocation of NF-kappa B into the nuclear compartment. However, the nature of the subunit involved in this mechanism has not been defined. To examine the mechanisms by which salicylates affect cytokine gene transcription, the amount of active and inactive NF-kappa B and NF-kappa B mRNA, in Porphyromonas gingivalis lipopolysaccharide-stimulated human monocytic cells was assessed. High doses of sodium salicylate suppressed NF-kappa B p65 mRNA accumulation, resulting in suppression of total NF-kappa B, p50 on tissue oligonucleotide had no effects on lipopolysaccharide-induced NF-kappa B activation. The data demonstrate that the p65 subunit of NF-kappa B is inhibited by salicylate treatment and highlight the role of salicylate in the control of gene expression of inflammatory mediators.

THIS POSITION PAPER WAS PREPARED BY THE Committee on Research, Science and Therapy of The American Academy of Periodontology and is intended for the information of the dental profession and the public. It represents a brief summary of the current state of knowledge about periodontal diseases in children and adolescents.

Inflamed gingival tissues are enriched in macrophages (MOs) and CD4-positive T cells; however, T helper-type cytokines such as interleukin (IL)-2 and IL-4 are absent. Therefore, we investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and MO persistence in the absence of exogenous IL-4. Gingival MOs, when compared with monocyte(MN)/MOs from peripheral blood mononuclear cells, expressed high levels of IL-4R mRNA. Furthermore, in vitro cultures of gingival MOs remained viable whereas identically treated peripheral blood MN/MOs rapidly lost viability. However, when gingival MOs were incubated with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced. When the frequency of apoptotic cells was assessed in rIL-4-treated gingival MO cultures, higher numbers of apoptotic cells were noted in rIL-4-treated versus control cultures. Furthermore, rIL-4-treated MOs from inflamed gingiva showed DNA fragmentation as assessed by electrophoresis. These findings clearly show that addition of exogenous rIL-4 to gingival MO cultures leads to cell death by apoptosis. This finding would suggest that topical application of rIL-4 may inhibit the persistence of MOs in adult periodontitis, which could then lead to decreased inflammation.

Previous studies have shown that the physical, biochemical, and antigenic properties of the bacterial outer membrane are profoundly influenced by the growth environment. In the present study, the effects of growth in hemin-replete (H+) and hemin-depleted (H-) media on the lipopolysaccharide (LPS) of the oral pathogen Porphyromonas gingivalis were investigated. Our studies show that LPS from P. gingivalis cultured in H+ media (H+LPS) expressed additional low-molecular-mass antigens, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis. Particularly evident was a 26-kDa antigen (26 LPSC) that was lost from the LPS upon transfer of P. gingivalis into H- media. The loss of the 26 LPSC was accompanied by a marked reduction in the hemin-binding capacity of the LPS. The 26 LPSC was refractory to Coomassie blue staining and proteinase K digestion. H+LPS from strain W50/BE1, a nonpigmented pleiotropic strain, lacked the 26 LPSC and did not bind hemin. Polyclonal antiserum raised to whole-cell antigens of P. gingivalis A7436, W83, and HG405 grown in H+ media, but not in H- media, recognized the 26 LPSC in the purified H+LPS from any of the three strains. The immunoreactivities of sera from humans with (n = 24) or without (n = 25) periodontitis to the 26 LPSC and other H+LPS determinants were analyzed by Western blot. Overall, 75% of adult periodontitis patient sera reacted with multiple bands in the H+LPS stepladder, particularly in the range of 14 to 27 kDa. In contrast, only 20% of control sera reacted faintly with H+LPS bands in the range 27 to 34 kDa. The 26 LPSC was recognized by over 40% of sera from adult patients with periodontitis and none of the healthy control sera. Taken together, these results suggest that the antigenicity and hemin-binding properties of P. gingivalis LPS can be modified by growth in H+ media.

The Papillon-Lefèvre syndrome (PLS) is a rare, autosomal recessive trait that is characterized by palmar plantar keratosis (PPK) and severe, early onset periodontitis, affecting both deciduous and permanent dentitions. The clinical presentation of PLS is variable; the disease occurs so infrequently as to limit clinical cases for study. The exception is a few families with extensive consanguinity in which numerous cases occur. Of particular interest to mapping the genetic origin of the syndrome is the co-expression of the major traits of hyperkeratosis and periodontitis, and their severity. In this paper, we report 2 families with multiple affected individuals from geographically remote areas. A large extended family, from the Cochin region of India, currently residing in Israel, in which there is documented consanguinity and a family from the southwest region of Germany. In each family, 1 individual presents with hyperkeratotic lesions with the complete absence of periodontal lesions. Further, the difference in severity of the hyperkeratotic lesions between families is marked, and one sibling in the German family expressed rapid, early onset periodontitis in the absence of PPK. The genetic nature and penetrance of the genetic defect are discussed.

One way prokaryotes respond to environmental stresses is by modifying selected outer membrane components. Iron, in the form of hemin, has been shown to be a significant regulator of Porphyromonas gingivalis growth and virulence and of the expression of outer membrane proteins and lipopoly saccharide. Since lipopoly saccharide has profound effects on host immune cells, this study compared the effect of hemin-restricted and hemin-normal P. gingivalis growth conditions on lipopolysaccharide priming of N-formylmethionyl-leucyl-phenylalanine-induced superoxide generation by human neutrophils. P. gingivalis was grown in a chemostat under normal (5 micrograms hemin/ml) and hemin-restricted (0.08 microgram hemin/ml) conditions. Purified lipopolysaccharide from both P. gingivalis normal and hemin-limited environments increased N-formylmethionyl-leucyl-phenylalanine-induced superoxide release by neutrophils in a dose-dependent manner. Lipopolysaccharide isolated from the hemin-normal conditions was a significantly more potent neutrophil priming agent than the lipopolysaccharide isolated from hemin-restricted conditions. Addition of normal human serum enhanced the priming effect of both lipopolysaccharide preparations; this effect, however, was more evident with the hemin-normal lipopolysaccharide. Further, this enhancing effect of serum was partly reduced in the presence of antibodies raised against the serum lipopolysaccharide-binding protein. The differences in the biological activity of the two lipopolysaccharide preparations could be associated with structural differences detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. These results indicate that hemin availability affects regulation of an aspect of P. gingivalis virulence, lipopolysaccharide-human neutrophils priming. The reduced capacity for neutrophil priming by hemin-restricted lipopolysaccharide appears to be related to lipopolysaccharide-neutrophil interactions and not to serum factors Targeting bacterial cell-surface components involved in hemin transport might be effective therapy for P. gingivalis-associated periodontal diseases.

Previous studies from our laboratory have demonstrated that freshly isolated peripheral blood monocytes from localized juvenile periodontitis (LJP) patients secrete more prostaglandin E2 (PGE2) after stimulation by lipopolysaccharide (LPS) than do monocytes from healthy subjects. However, it is not clear if the altered function of LJP monocytes is intrinsic to the cells or is induced by the persistent infection of the periodontium. The present study was designed to compare PGE2 secretion by freshly-isolated peripheral blood monocytes (FIM) from LJP and control subjects to in vitro monocyte-derived macrophages (MDM) from the same subjects. We also examined monocyte maturation into macrophage-like cells and the cell-surface expression of the LPS, receptor, CD14 during the culture period. FIM from LJP patients and controls were stimulated by different concentrations of LPS (O to 30 micrograms/ml) for 24 hours. These experiments were performed immediately after cell separation and after 10 days in culture, which allowed differentiation of monocytes into MDM. PGE2 levels in the culture media were determined using a radioimmunoassay. Cell surface expression of CD71, a cell maturation marker, and CD14 were assayed by cell-ELISA in relation to beta-2-microglobulin. LPS-stimulated FIM from LJP patients secreted 3 to 4 times more PGE2 than control FIM at all LPS concentrations tested. After 10 days in culture, the LJP MDM secretion of PGE2 reduced to control MDM level of PGE2 secretion. These levels of PGE2 secretion were comparable to PGE2 secretion from FIM of controls. Cell maturation, as verified by CD71 expression, was found not to differ between the groups. However, the expression of CD14 by LJP FIM was much lower than on control FIM (approximately equal to 50%). After 5 or 10 days in culture, MDM from both control and LJP subjects expressed comparable amounts of CD14. The results suggest that in vitro conditions reverse the hypersensitivity of LJP monocytes to LPS into control levels and CD14 expression is not correlated to the hyper-responsiveness of the cells to LPS.

A review of phagocytic cells-polymorphonuclear leukocytes and monocytes-in the inflammatory process is presented. Examples of phagocyte defect-related pathology serve as a framework for understanding the role of these cells in periodontal infection. The role of alterations in neutrophil function in localized juvenile periodontitis is presented as a model system for understanding periodontal pathology as a result of host-related functional abnormalities. Two topical alternative hypotheses for periodontal breakdown are presented in which. macrophage control of the chronic lesion is altered by an absence of T cells or the influence of bacterial superantigens. J Periodontol 1996;67:1070-1075.