Search

Made available in DSpace on 2019-10-06T16:46:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by extensive inflammation, demyelination, axonal loss and gliosis. Evidence indicates that mast cells contribute to immunopathogenesis of both MS and experimental autoimmune encephalomyelitis (EAE), which is the most employed animal model to study this disease. Considering the inflammatory potential of mast cells, their presence at the CNS and their stabilization by certain drugs, we investigated the effect of ketotifen fumarate (Ket) on EAE development. EAE was induced in C57BL/6 mice by immunization with MOG35-55 and the animals were injected daily with Ket from the seventh to the 17th day after disease induction. This early intervention with Ket significantly reduced disease prevalence and severity. The protective effect was concomitant with less NLRP3 inflammasome activation, rebalanced oxidative stress and also reduced T cell infiltration at the CNS. Even though Ket administration did not alter mast cell percentage at the CNS, it decreased the local CPA3 and CMA1 mRNA expression that are enzymes typically produced by these cells. Evaluation of the CNS-barrier permeability indicated that Ket clearly restored the permeability levels of this barrier. Ket also triggered an evident lymphadenomegaly due to accumulation of T cells that produced higher levels of encephalitogenic cytokines in response to in vitro stimulation with MOG. Altogether these findings reinforce the concept that mast cells are particularly relevant in MS immunopathogenesis and that Ket, a known stabilizer of their activity, has the potential to be used in MS control. Department of Microbiology and Immunology Institute of Biosciences São Paulo State University (UNESP), Rua Dr. Plinio Pinto e Silva, S/N, Distrito de Rubião Júnior Department of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (UNESP) Department of Surgery Stomatology Pathology and Radiology Bauru School of Dentistry University of São Paulo (USP) Department of Microbiology and Immunology Institute of Biosciences São Paulo State University (UNESP), Rua Dr. Plinio Pinto e Silva, S/N, Distrito de Rubião Júnior Department of Chemistry and Biochemistry Institute of Biosciences São Paulo State University (UNESP)

We have identified impaired neutrophils in elderly individuals which could be involved with Candida-related denture stomatitis (DS), an oral infection predominantly caused by Candida albicans, affecting especially elderly individuals using dental prosthesis. However, specific mechanisms performed by neutrophil contributing to the susceptibility of the elderly to DS are not fully understood. This study evaluated activation features of blood neutrophils from elderly and young individuals with DS. Blood neutrophils cultured with C. albicans from elderly subjects secreted decreased levels of CXCL8. However, C. albicans challenged-neutrophils from DS patients produced high IL-4 and IL-10, and low GM-CSF levels, regardless of age. Additional elastase activity of neutrophils from both elderly groups was detected after incubation with C. albicans, but only neutrophils from elderly DS demonstrated high myeloperoxidase activity. Therefore, DS patients have affected neutrophils, and the advance of age intensifies these damages. In summary, individuals with Candida-related denture stomatitis presented variation in the neutrophil phenotype and activation. Such alterations were more intense in neutrophils from infected elderly individuals.

The immunopathologic and inflammatory mechanisms involved in periodontal disease (PD) include the participation of host resident, inflammatory cells and chemical mediators. Metalloproteinases (MMPs) and nitric oxide (NO) play essential role in extracellular matrix turnover of periodontal tissue destruction. In this study, by means of RT-PCR through semi-quantitative densitometric scanning methods, the expression of MMPs -2 and -9 and inducible NO synthase (iNOS) was temporally and spatially investigated during the destructive mechanisms of experimentally induced PD in rats. Samples from different periods were microscopically analyzed and compared with the contralateral side (control). Our results showed significant expression of MMP-9 and iNOS in tissues affected by PD, as compared with controls, three days after PD induction, simultaneously with the beginning of alveolar bone loss. At 7 days post induction, only the MMP-9 mRNA presented a significantly higher expression, as compared with the respective controls. Thus, in the rat ligature-induced PD, MMP-9 and iNOS might importantly participate in the early stages of the disease, including inflammatory cell migration, tissue destruction and alveolar bone resorption. Also, we may suggest that the exuberant presence of PMNs may be related to the important expression of iNOS and MMP-9 found at 3 days post induction.

Dentin is a reservoir of several potentially active molecules, and dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) are the two major non-collagenous proteins. It has been established that dentin molecules are released as a consequence of osteoclast action during the resorption process. Along with osteoclasts, inflammatory cells seem to play an important role at sites of root resorption. Although the role of dentin molecules in dentinogenesis is well known, their role in pathological processes associated with dentin matrix dissolution is unclear. Recent studies have suggested that dentin components may function as chemotactic and activator signals for inflammatory cells at these sites. Herein we present evidence that demineralized dentin crude extract, DSP, and DPP induced doseand time-dependent neutrophil migration into the peritoneal cavity of mice and that this activity was inhibited by dexamethasone, but not by indomethacin or MK886. The blockade of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) receptors inhibited neutrophil accumulation. The neutrophil migration was also diminished in the absence of the chemokines cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein-2 (MIP-2), but not in the absence of macrophage inflammatory protein-1alpha (MIP-1alpha). These results demonstrate that dentin induces neutrophil migration via the synthesis of IL-1beta, TNF-alpha, and chemokines and they suggest that dentin matrix proteins may have an active role in inflammatory cell recruitment during pathological processes associated with dentin and bone matrix dissolution.