Biomedical subjects

D T Graves

Publications and source records attributed to D T Graves.

At least 19 recordsLinked to original sources

PubMed2006

Diabetes-enhanced inflammation and apoptosis--impact on periodontal pathology.

Diabetes, particularly type 2 diabetes, is a looming health issue with many ramifications. Because diabetes alters the cellular microenvironment in many different types of tissues, it causes myriad untoward effects, collectively referred to as 'diabetic complications'. Two cellular processes affected by diabetes are inflammation and apoptosis. This review discusses how diabetes-enhanced inflammation and apoptosis may affect the oral environment. In particular, dysregulation of tumor necrosis factor and the formation of advanced glycation products, both of which occur at higher levels in diabetic humans and animal models, potentiate inflammatory responses and induce apoptosis of matrix-producing cells. The enhanced loss of fibroblasts and osteoblasts through apoptosis in diabetics could contribute to limited repair of injured tissue, particularly when combined with other known deficits in diabetic wound-healing. These findings may shed light on diabetes-enhanced risk of periodontal diseases.

Apoptosis↗

PubMed2006

Diabetes enhances periodontal bone loss through enhanced resorption and diminished bone formation.

Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9-fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.

Alveolar Bone Loss↗

PubMed2005

Tumor necrosis factor alpha (TNF-alpha) coordinately regulates the expression of specific matrix metalloproteinases (MMPS) and angiogenic factors during fracture healing.

Recent studies from our laboratory demonstrate that TNF-alpha signaling contributes to the regulation of chondrocyte apoptosis and a lack of TNF-alpha signaling leads to a persistence of cartilaginous callus and delayed resorption of mineralized cartilage. This study examines how delays in the endochondral repair process affect the expression of specific mediators of proteolytic cartilage turnover and vascularization. Simple closed fractures were produced in wild type and TNF-alpha receptor (p55-/-/p75-/-)-deficient mice. Using ribonuclease protection assay (RPA) and microarray analysis, the expression of multiple mRNAs for various angiogenic factors and the metalloproteinase gene family were measured in fracture calluses. The direct actions of TNFalpha on the expression of specific angiogenic factors and metalloproteinases (MMPs) was examined in both cultured callus cells and articular chondrocytes to compare the effects of TNF-alpha in growth cartilage versus articular cartilage. MMPs 2, 9, 13, and 14 were quantitatively the most prevalent metalloproteases and all showed peaks in expression during the chondrogenic period. In the absence of TNF-alpha signaling, the expression of all of these mRNAs was reduced. The angiopoietin families of vascular regulators and their receptors were expressed at much higher levels than the VEGFs and their receptors and while the angiopoietins showed diminished or delayed expression in the absence of TNF-alpha signaling, VEGF and its receptors remained unaltered. The expression of vascular endothelial growth inhibitor (VEGI or TNFSF15) showed a near absence in its expression in the TNF-alpha receptor-deficient mice. In vitro assessment of cultured fracture callus cells in comparison to primary articular chondrocytes showed that TNF-alpha treatment specifically induced the expression of MMP9, MMP14, VEGI, and Angiopoietin 2. These results suggest that TNF-alpha signaling in chondrocytes controls vascularization of cartilage through the regulation of angiopoietin and VEGI factors which play counterbalancing roles in the induction of growth arrest, or apoptosis in endothelial cells. Furthermore, TNF-alpha appears to regulate, in part, the expression of two key proteolytic enzymes, MMP 9 and MMP14 that are known to be crucial to the progression of vascularization and turnover of mineralized cartilage. Thus, TNF-alpha signaling in healing fractures appears to coordinate the expression of specific regulators of endothelial cell survival and metalloproteolytic enzymes and is essential in the transition and progression of the endochondral phase of fracture repair.

Angiogenic Proteins↗

PubMed2005

Inflammation is more persistent in type 1 diabetic mice.

Whether diabetes enhances or diminishes the host response to bacteria has been controversial. To determine how diabetes alters the inflammatory response, we inoculated P. gingivalis into the scalps of mice rendered diabetic with multiple low-dose streptozotocin treatment. On day 1, a moderate to severe inflammatory infiltrate was noted in both the diabetic and normoglycemic mice. After 3 days, the inflammatory infiltrate was significantly higher in the diabetic compared with the control group (P < 0.05). The mRNA expression of chemokines macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 was strongly and similarly induced 3 hrs and 1 day post-inoculation. By day 3, the levels were reduced in normoglycemic mice but remained significantly higher in the diabetic group (P < 0.05). To determine whether persistent inflammation was specific for the streptozotocin-induced diabetic model, we directly compared the expression of TNF-alpha in streptozotocin-induced and db/db diabetic mice, which developed type 2 diabetes. Both exhibited prolonged TNF-alpha expression compared with controls. These results suggest that diabetes alters bacteria-host interactions by prolonging the inflammatory response.

Animals↗

PubMed2004

Apoptotic effects of LPS on fibroblasts are indirectly mediated through TNFR1.

During periods of periodontal attachment loss, one of the most significant cellular changes is a decrease in the number of fibroblasts. We previously demonstrated that LPS induces apoptosis of fibroblastic cells in vivo, largely through TNF-alpha. We conducted in vivo experiments by subcutaneous inoculation of LPS in wild-type, TNFR1-/-R2-/-, TNFR1-/-, and TNFR2-/- mice to identify which TNF receptors are involved and the specific caspase pathway activated. LPS stimulated apoptosis through TNFR1 but not TNFR2, which was accompanied by the induced expression of 12 apoptotic genes. Fluorometric studies demonstrated that LPS in vivo significantly increased caspase-8 and caspase-3 activity, which was also dependent on TNF receptor signaling. By the use of specific caspase inhibitors, caspases-3 and -8 were shown to play an important role in LPS-induced apoptosis in vivo. Thus, LPS acts through TNFR1 to modulate the expression of apoptotic genes and activate caspases-3 and -8.

Animals↗

PubMed2003

Impaired fracture healing in the absence of TNF-alpha signaling: the role of TNF-alpha in endochondral cartilage resorption.

UNLABELLED: TNF-alpha is a major inflammatory factor that is induced in response to injury, and it contributes to the normal regulatory processes of bone resorption. The role of TNF-alpha during fracture healing was examined in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. The results show that TNF-alpha plays an important regulatory role in postnatal endochondral bone formation. INTRODUCTION: TNF-alpha is a major inflammatory factor that is induced as part of the innate immune response to injury, and it contributes to the normal regulatory processes of bone resorption. METHODS: The role of TNF-alpha was examined in a model of simple closed fracture repair in wild-type and TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice. Histomorphometric measurements of the cartilage and bone and apoptotic cell counts in hypertrophic cartilage were carried out at multiple time points over 28 days of fracture healing (n = 5 animals per time point). The expression of multiple mRNAs for various cellular functions including extracellular matrix formation, bone resorption, and apoptosis were assessed (triplicate polls of mRNAs). RESULTS AND CONCLUSIONS: In the absence of TNF-alpha signaling, chondrogenic differentiation was delayed by 2-4 days but subsequently proceeded at an elevated rate. Endochondral tissue resorption was delayed 2-3 weeks in the TNF-alpha receptor (p55(-/-)/p75(-/-))-deficient mice compared with the wild-type animals. Functional studies of the mechanisms underlying the delay in endochondral resorption indicated that TNF-alpha mediated both chondrocyte apoptosis and the expression of proresorptive cytokines that control endochondral tissue remodeling by osteoclasts. While the TNF-alpha receptor ablated animals show no overt developmental alterations of their skeletons, the results illustrate the primary roles that TNF-alpha function contributes to in promoting postnatal fracture repair as well as suggest that processes of skeletal tissue development and postnatal repair are controlled in part by differing mechanisms. In summary, these results show that TNF-alpha participates at several functional levels, including the recruitment of mesenchymal stem, apoptosis of hypertrophic chondrocytes, and the recruitment of osteoclasts function during the postnatal endochondral repair of fracture healing.

Animals↗

PubMed2003

The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction.

Interleukin (IL)-1 and tumor necrosis factor (TNF) represent proinflammatory cytokines that stimulate a number of events which occur during periodontal disease. These include the induction of adhesion molecules and other mediators that facilitate and amplify the inflammatory response, the stimulation of matrix metalloproteinase, and bone resorption. The activity of these cytokines coincides with the critical events that occur during periodontal disease, namely, loss of attachment and bone resorption. The use of antagonists to IL-1 and TNF in experimental periodontitis have demonstrated a cause-and-effect relationship between the activity of these cytokines and the spread of an inflammatory front to deeper areas in the connective tissue, loss of connective tissue attachment, osteoclast formation, and loss of alveolar bone. In addition, the loss of fibroblasts that occurs during infection with periodontal pathogens is, in part, mediated by TNF. Thus, much of the damage that occurs during periodontal tissue destruction can be attributed to IL-1 and TNF activity. This destruction may very well represent an overreaction of the host response to periodontal pathogens caused by excessive production of IL-1 and TNF.

Alveolar Bone Loss↗

PubMed2002

Developmentally regulated monocyte recruitment and bone resorption are modulated by functional deletion of the monocytic chemoattractant protein-1 gene.

Tooth eruption involves the movement of a tooth from its site of development within the alveolar bone to its functional position in the oral cavity. Because this process is dependent upon monocytes and formation of osteoclasts, it represents an excellent model for examination of these processes under developmental regulation. We investigated the functional role of monocyte chemoattractant protein-1 (MCP-1) in monocyte recruitment and its impact on bone resorption by examining each parameter in MCP-1(-/-) mice as compared with wild-type controls during tooth eruption. The peak number of monocytes occurred on day 5 in the MCP-1(-/-) mice and on day 9 in the wild-type mice. The peak number of osteoclasts followed the same pattern, occurring sooner in the MCP-1(-/-) (day 5) than in wild-type mice (day 9). Consistent with this, MCP-1(-/-) mice had an accelerated rate of tooth eruption in the early phase when the teeth first entered the oral cavity as compared with the wild-type mice. However, there was accelerated eruption in the wild-type group in the later phase of tooth eruption. When examined at the molecular level, inducible nitric oxide synthase (iNOS) and interleukin-11 and -6 were expressed at considerably higher levels in the experimental group with accelerated tooth eruption. This is the first report identifying these factors as potential modulators of bone resorption that can accelerate the rate of tooth eruption. We conclude that, at early timepoints, monocyte recruitment occurs by MCP-1-independent mechanisms. However, at a later timepoint, MCP-1 may play a contributory role in the recruitment of monocytic cells, allowing the wild-type animals to catch up.

Animals↗

PubMed2002

Clinical, radiographic and biochemical assessment of IL-1/TNF-alpha antagonist inhibition of bone loss in experimental periodontitis.

OBJECTIVES: To assess clinical, radiographic, and biochemical markers as diagnostic indicators of disease activity by comparing ligature-induced bone loss in the presence or absence of IL-1/TNF-alpha antagonist inhibition of bone loss in a primate model. MATERIAL AND METHODS: 6 animals with a naturally-occurring gingivitis were evaluated over a 6-week time period following the placement of silk ligatures and initiation of a soft diet. Three animals received intrapapillary injections of soluble receptors (blockers), capable of blocking the biologic activity for both IL-1 and TNF-alpha, and 3 animals received vehicle (control) injections. Injections were given 3X per week over the course of the study. Clinical assessments included a gingival index and quantification of gingival crevicular fluid (GCF) levels. Collected GCF samples were then used in the biochemical assessment of pyridinoline (PYD) and bone alkaline phosphatase (BAP). Radiographic assessment was made using computer-assisted subtraction radiography to measure both bone density (CADIA) values and linear changes in crestal bone height. RESULTS: Significant (p<0.01) changes using both radiographic measures occurred between 2 and 4 weeks following initiation of disease in this model. The use of the blockers significantly (p<0.01) reduced the levels of radiographic bone loss by approximately 50% over that found in the control sites. Both biochemical markers showed the greatest increase during the first two weeks of the study with PYD levels increased 35-fold over baseline levels after 1 week. This difference in response was significantly (p<0.05) greater than the levels found in the non-ligated teeth or in the ligated teeth receiving blockers injections. BAP levels showed significant increases in ligated teeth compared to non-ligated teeth, but failed to show any significant differences between animals treated with vehicle and those treated with IL-1/TNF antagonists. In contrast to these radiographic and biochemical effects, there were no significant differences detected between animals treated with antagonists and the control group for any of the clinical measures. CONCLUSIONS: The results of this study demonstrate that both subtraction radiography and PYD crevicular fluid levels can detect relative differences in periodontal disease progression, while BAP crevicular fluid levels cannot.

Alkaline Phosphatase↗

PubMed2002

Mice lacking monocyte chemoattractant protein 1 have enhanced susceptibility to an interstitial polymicrobial infection due to impaired monocyte recruitment.

Monocyte chemoattractant protein 1 (MCP-1) is an important chemokine that induces monocyte recruitment in a number of different pathologies, including infection. To investigate the role of MCP-1 in protecting a host from a chronic interstitial polymicrobial infection, dental pulps of MCP-1(-/-) mice and controls were inoculated with six different oral pathogens. In this model the recruitment of leukocytes and the impact of a genetic deletion on the susceptibility to infection can be accurately assessed by measuring the progression of soft tissue necrosis and osteolytic lesion formation. The absence of MCP-1 significantly impaired the recruitment of monocytes, which at later time points was threefold higher in the wild-type mice than in MCP-1(-/-) mice (P < 0.05). The consequence was significantly enhanced rates of soft tissue necrosis and bone resorption (P < 0.05). We also determined that the MCP-1(-/-) mice were able to recruit polymorphonuclear leukocytes (PMNs) to a similar or greater extent as controls and to produce equivalent levels of Porphyromonas gingivalis-specific total immunoglobulin G (IgG) and IgG1. These results point to the importance of MCP-1 expression and monocyte recruitment in antibacterial defense and demonstrate that antibacterial defense is not due to an indirect effect on PMN recruitment or modulation of the adaptive immune response.

Animals↗

PubMed2002

Tumor necrosis factor modulates apoptosis of monocytes in areas of developmentally regulated bone remodeling.

Tooth eruption is characterized by spatially segregated bone resorption along the path of eruption and bone formation in the opposite direction. Monocyte recruitment occurs in two distinct peaks in both areas of resorption and formation. Without such recruitment tooth eruption does not occur. The signals that regulate this recruitment are thought to involve the expression of cytokines and chemokines. One such cytokine is tumor necrosis factor (TNF), which can affect monocyte recruitment through the induction of chemokines and adhesion molecules and increase their lifespan by acting as antiapoptotic cell survival signals. We examined the latter by studying mice with targeted deletions of TNF receptors p55 and p75 (TNFRp55/p75). The results indicate that mice that lack functional TNF receptors have a significantly reduced number of monocytes in the apical area associated with bone formation. The reduced number of monocytes in this area can be accounted for by an increase in apoptosis in TNFRp55-/-/p75-/-. In contrast, the number of monocytes, the rate of monocyte apoptosis, and the formation of osteoclasts in the occlusal area associated with bone resorption occurred independently of TNF activity. These results suggest that TNF receptor signaling can affect tooth eruption by acting as a monocyte survival signal in some but not all areas of bone undergoing developmentally regulated remodeling.

Animals↗

PubMed2001

IL-1 plays a critical role in oral, but not dermal, wound healing.

Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. After injury, proinflammatory cytokines act as important modulators of the inflammatory process. IL-1 expression has been regarded as necessary for healing; however, its effects have also been implicated in delayed wound repair. Currently, there is no consensus or direct evidence that IL-1 activity plays a central role in the healing process. The present investigation was undertaken to define the role of IL-1R signaling in the healing outcome of an excisional wound in the palate or scalp of mice that had targeted deletions of the IL-1R type 1 (IL-1R1(-/-)) compared with matched wild-type mice. Histomorphometric analysis was undertaken to assess the degree of healing and the recruitment of polymorphonuclear and mononuclear phagocytes. After 14 days, wild-type mice exhibited complete closure of intraoral wounds, while IL-1R1(-/-) animals had only partial closure (50%). In the IL-1R1(-/-) mice, healing tissues exhibited a persistent inflammatory cell infiltrate, which did not occur in wild-type animals. Treatment with antibiotics significantly diminished the persistent inflammatory infiltrate and improved healing in the experimental animals. In contrast to oral wounds, the rate of healing and recruitment of polymorphonuclear cells in scalp wounds was similar in IL-1R1(-/-) and wild-type mice. The present data underscore the importance of IL-1 in wound healing in a challenging environment and identify its principal role in facilitating the healing process by protecting an open wound from bacterial insult. In a less challenging environment, the production of new connective tissue and its coverage by migrating epithelium are minimally affected by the absence of IL-1 activity.

Animals↗

PubMed2001

Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibits loss of tissue attachment in experimental periodontitis.

BACKGROUND, AIMS: Periodontal disease is a significant cause of tooth loss among adults and is characterized by the alteration and permanent destruction of the deeper periodontal tissues. Although the presence of pathologic microbes is required to trigger this process, the amplification and progression of the diseased state is believed to rely heavily on the production of host mediators in response to bacteria or their metabolic products. The inflammatory response is effective in preventing large-scale colonization of the gingival tissues by bacteria that lie in close proximity to the tooth surface or within the gingival sulcus. It has been postulated that the host-response in some individuals may lead to an over-reaction to invading oral pathogens resulting in the destruction of periodontal tissues. METHODS: Several host-derived mediators are believed to contribute to this response. Two agents considered to be essential in periodontal destruction are interleukin-1 (IL-1) and tumor necrosis factor (TNF). We investigated the role of IL-1 and TNF in the loss of connective tissue attachment in a Macaca fascicularis primate model of experimental periodontitis. Silk ligatures impregnated with the periodontal pathogen, Porphyromonas gingivalis were wrapped around the posterior teeth and the activity of IL-1 and TNF were inhibited by soluble receptors to these proinflammatory cytokines via local injection into interdental papillae. RESULTS: Histomorphometric analysis indicates that IL-1 and TNF antagonists significantly reduced the loss of connective tissue attachment by approximately 51% and the loss of alveolar bone height by almost 91%, both of which were statistically significant. CONCLUSION: This investigation demonstrates that the loss of connective tissue attachment and progression of periodontal disease can be retarded by antagonists to specific host mediators such as IL-1 and TNF and may provide a potential treatment modality to combat the disease process.

Alveolar Bone Loss↗

PubMed2001

Tumor necrosis factor modulates fibroblast apoptosis, PMN recruitment, and osteoclast formation in response to P. gingivalis infection.

P. gingivalis is an important oral pathogen, which has been closely linked to periodontal disease as well as lesions of endodontic origin. Both infections are associated with a decrease in fibroblast numbers, formation of an inflammatory infiltrate, and bone resorption. The goal of this study was to investigate the role that the host response plays in the capacity of P. gingivalis to stimulate fibroblast apoptosis, PMN recruitment, and osteoclastogenesis. This was accomplished by the use of an in vivo calvarial model in mice with targeted deletion of TNF receptors p55 and p75 and matched wild-type mice. The results indicate that P. gingivalis induces fibroblast apoptosis in vivo and establish for the first time that this involves the stimulation of a host response. Moreover, bacteria-stimulated PMN recruitment and osteoclastogenesis were also dependent upon the host response. The results suggest that much of the damage caused by P. gingivalis infection, including fibroblast apoptosis, at least under some circumstances, results from stimulation of the host response rather than the direct effect of bacterial products. Furthermore, this may represent a more general mechanism by which bacterial challenge induces apoptosis of matrix-producing cells through the induction of TNF.

Animals↗

PubMed2000

Interleukin-1 receptor signaling rather than that of tumor necrosis factor is critical in protecting the host from the severe consequences of a polymicrobe anaerobic infection.

Infection of the dental pulp leads to an osteolytic lesion that results from a polymicrobial infection consisting largely of pathogenic anaerobes. Infection causes significant morbidity and mortality mediated by bacterial factors and in some cases by the up-regulation of inflammatory cytokines. The inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF), in particular, play a complex and central role in the responses to microbial pathogens. However, relatively little is known about the significance of these cytokines in protecting the host from focal polymicrobial anaerobic infections. To establish the relative importance of IL-1 and TNF in mediating the response to a mixed anaerobic infection, we inoculated the dental pulp of mice with six anaerobic pathogens containing functional deletions of receptors to IL-1 (IL-1R1(-/-)), TNF (TNFRp55(-/-)-p75(-/-)), or both (TNFRp55(-/-)-IL-1RI(-/-)). The results indicate that IL-1 receptor signaling and TNF receptor signaling both play similarly important roles in protecting the host from local tissue damage. However, IL-1 receptor signaling is considerably more important than TNF receptor signaling in preventing the spread of infection into surrounding fascial planes, since IL-1R1(-/-) but not TNFRp55(-/-)-p75(-/-) mice exhibited significantly higher morbidity and mortality. Moreover, all of the fatal infections occurred in male mice, suggesting the importance of gender differences in limiting the impact of these infections.

Abscess↗

PubMed1999

The expression of monocyte chemoattractant protein-1 and other chemokines by osteoblasts.

Chemokines are low molecular weight secretory proteins that function principally as stimulators of leukocyte recruitment. There are four defined chemokine subfamilies based on their primary structure, CXC, CC, C and CX3C. Members of the CC chemokine subfamily, a such as monocyte chemoattractant protein 1 (MCP-1) are chemotactic for monocytes and other leukocyte subsets. Because monocytes produce factors that regulate bone formation or resorption, such as PDGF, IL-1 or TNF, chemokines that initiate their recruitment are likely to be important in regulating osseous metabolism. In the studies below, data is presented demonstrating mechanisms of MCP-1 expression in osteoblastic cells. These studies establish that MCP-1 is induced during osseous inflammation and in developmentally regulated bone remodelling, and is associated with enhanced monocyte recruitment when applied to osseous lesions.

Animals↗

PubMed1999

Interleukin-1 and tumor necrosis factor receptor signaling is not required for bacteria-induced osteoclastogenesis and bone loss but is essential for protecting the host from a mixed anaerobic infection.

Bacterial infection causes significant morbidity, mediated in part by the up-regulation of inflammatory cytokines. Cytokine induction is thought to stimulate osteolysis in conditions such as periodontal disease and otitis media. To establish the relative importance of interleukin-1 (IL-1) and tumor necrosis factor (TNF) in mediating the response to a mixed anaerobic infection, we used an in vivo model in which the dental pulp was inoculated with six anaerobic pathogens, in mice with functional deletions of receptors to IL-1 (IL-1RI(-/-)), TNF (TNFRp55(-/-)-p75(-/-)), or both (TNFRp55(-/-)-IL-1RI(-/-)). Polymorphonuclear and mononuclear phagocyte recruitment occurred to the greatest extent in TNFRp55(-/-)-IL-1RI(-/-) mice, and to a lesser extent in IL-1RI(-/-) or TNFRp55(-/-)-p75(-/-) mice, and the least in wild-type mice, demonstrating that recruitment of these phagocytes is not dependent on IL-1 or TNF receptor signaling. A similar pattern was observed for bacterial penetration into host tissue. Because it had recently been reported that TNF played a critical role in mediating lipopolysaccharide-induced bone loss, we anticipated that mice with targeted deletions of TNFRp55(-/-) would have reduced osteoclastogenesis. Surprisingly, osteolytic lesion formation was greatest in animals lacking TNF and/or IL-1 receptors. These results indicate that IL-1 or TNF receptor signaling is not required for bacteria-induced osteoclastogenesis and bone loss, but does play a critical role in protecting the host against mixed anaerobic infections.

Animals↗

PubMed1999

The potential role of chemokines and inflammatory cytokines in periodontal disease progression.

Inflammation is regulated by the expression of mediators that cause a number of pleiotropic events culminating in the recruitment of inflammatory cells and release of biologic mediators by leukocytes. If the inflammation is transient in nature, it can protect the host by activating defense mechanisms and initiating wound repair. However, if the inflammation is inappropriate, it can lead to considerable tissue damage. My colleagues and I have investigated the role of chemokines, particularly monocyte chemoattractant protein 1, in various pathological processes and the role of the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF) in experimental periodontitis. I will discuss first the studies on chemokines and then the use of IL-1 and TNF blockers in inhibiting inflammation and bone loss in the periodontium.

Chemokine CCL2↗