Characterization of cytokines, matrix metalloproteinases and toll-like receptors in human periodontal tissue destruction

Periodontal Disease affects the supporting structures of the teeth and is initiated by a microbial biofilm called dental plaque. Severity ranges from superficial inflammation of the gingiva (gingivitis) to extensive destruction of connective tissue and bone leading to tooth loss (periodontitis). In periodontitis the destruction of tissue is caused by a cascade of microbial and host factors together with proteolytic enzymes. Matrix metalloproteinases (MMPs) are known to be central mediators of the pathologic destruction in periodontitis. Initially plaque bacteria provide pathogen-associated molecular patterns (PAMPs) which are sensed by Toll-like receptors (TLRs), and initiate intracellular signaling cascades leading to host inflammation. Our aim was to characterize TNF-α (tumor necrosis factor-alpha) and its type I and II receptors in periodontal tissues, as well as, the effects of TNF-α, IL-1β (interleukin-1beta) and IL-17 on the production and/or activation of MMP-3, MMP-8 and MMP-9. Furthermore we mapped the TLRs in periodontal tissues and assessed how some of the PAMPs binding to the key TLRs found in periodontal tissues affect production of TNF-α and IL-1β by gingival epithelial cells with or without combination of IL-17. TNF-α and its receptors were detected in pericoronitis. Furthermore, increased expression of interleukin-1β and vascular cell adhesion molecule-1 was found as a biological indicator of TNF-α ligand-receptor interaction. MMP-3, -8, and 9 were investigated in periodontitis affected human gingival crevicular fluid and gingival fibroblasts produced pro-MMP-3. Following that, the effect of IL-17 was studied on MMP and pro-inflammatory cytokine production. IL-17 was increased in periodontitis and up-regulated IL-1β, TNF-α, MMP-1 and MMP-3. We continued by demonstrating TLRs in gingival tissues, in which significant differences between patients with periodontitis and healthy controls were found. Finally, enzyme-linked immunosorbent assays were performed to show that the gingival cells response to inflammatory responses in a TLR-dependent manner. Briefly, this thesis demonstrates that TLRs are present in periodontal tissues and present differences in periodontitis compared to healthy controls. The cells of gingival tissues respond to inflammatory process in a TLR-dependent manner by producing pro-inflammatory cytokines. During the destruction of periodontal tissues, the release (IL-1β and TNF-α) and co-operation with other pro-inflammatory cytokines (IL-17), which in turn increase the inflammation and thus be more harmful to the host with the increased presence of MMPs (MMP-1, MMP-3, MMP-8, MMP-9) in diseased over healthy sites.Parodontaalisairaudet on hampaiden kiinnityskudostulehduksia, jotka johtuvat hampaiden mikrobibiofilmin kerääntymisestä hammasplakiksi. Vakavuudeltaan sairaudet vaihtelevat pinnallisesta ientulehduksesta (gingiviitti) kiinnityskudon ja luun tuhoutumiseen ja hampaan irtoamiseen johtavaan kiinnityskudostulehdukseen (parodontiitti). Parodontiittiin liittyvä kudostuho johtuu sekä bakteeri- että isäntäperäisistä tekijöistä yhdessä proteolyyttisten entsyymien kanssa. Matriksin metalloproteinaasit (MMP) ovat keskeisiä tekijöitä parodontiitin patologisessa kudostuhossa. Hammasplakin bakteerit ilmentävät patogeeneihin liittyviä molekyylirakenteita (pathogen-associated molecular patterns, PAMPs), joita toll-like-reseptorit (TLRs) tunnistavat ja solunsisäinen signaalireitti isännän tulehdusreaktiossa alkaa. Työn tavoitteena oli karakterisoida TNF-α (tumor necrosis factor-alpha) ja sen tyyppi I ja II reseptorit parontaalikudoksessa. Lisäksi tutkimme TNF- α:n, IL-1β:an (interleukiini-1-beetta) ja IL-17:sta (interleukiini-17) vaikutuksia MMP-3:en, MMP-8:an ja MMP-9:än tuottoon ja /tai aktivaatioon. Kartoitimme TLR:eita parodontaalikudoksessa ja tutkimme, kuinka eräiden PAMP:ien sitoutuminen kohde-TLR:ään vaikuttaa ikenen epiteelisolujen TNF- α:n ja IL-1β:an tuottoon yhdessä ja erikseen IL-17:sta kanssa. Tulokset osoittivat, että parodontaalikudokset ilmentävät TLR:eita tasoilla, jotka eroavat parodontaalisesti sairaiden ja terveiden välillä. Ienkudoksen solut reagoivat tulehdukseen TLR-riippuvaisesti tuottamalla tulehdusvälittäjäaineita, TNF-α ja IL-1β. Parodontiitissa tulehdusvälittäjäaineiden tuotanto ja niiden yhteistoiminta IL-17:sta kanssa voimistaa isännälle haitallista tulehdureaktiota, jossa myös vapautuu enemmän MMP:eja (MMP-1, MMP-3, MMP-8 ja MMP-9) verrattuna terveisiin henkilöihin. Tutkimuksen perimmäinen tarkoitus on kerätä tietoa mahdollisia uusia hoitomenetelmiä varten, jotka olisivat turvallisia, tehokkaita, huokeita ja johtaisivat vähäisiin haittavaikutuksiin ihmisillä, jotka kärsivät suun tulehduksista

Recent activity of the Be/X-ray binary system SAX J2103.5+4545

Aims. We present a multiwavelength study of the Be/X-ray binary system SAX J2103.5+4545 with the goal of better characterizing the transient behaviour of this source. Methods. SAX J2103.5+4545 was observed by Swift-XRT four times in 2007 from April 25 to May 5, and during quiescence in 2012 August 31. In addition, this source has been monitored from the ground-based astronomical observatories of El Teide (Tenerife, Spain), Roque de los Muchachos (La Palma, Spain) and Sierra Nevada (Granada, Spain) since 2011 August, and from the TUBITAK National Observatory (Antalya, Turkey) since 2009 June. We have performed spectral and photometric temporal analyses in order to investigate the different states exhibited by SAX J2103.5+4545. Results. In X-rays, an absorbed power law model provided the best fit for all the XRT spectra. An iron-line feature at ~6.42 keV was present in all the observations except for that taken during quiescence in 2012. The photon indexes are consistent with previous studies of SAX J2103.5+4545 in high/low luminosity states. Pulsations were found in all the XRT data from 2007 (2.839(2) mHz; MJD 54222.02), but not during quiescence. Both optical outbursts in 2010 and 2012 lasted for about 8/9 months (as the one in 2007 probably did and the current one in 2014 might do) and were most probably caused by mass ejection events from the Be star that eventually fed the circumstellar disc. All of these outbursts started about 3 months before the triggering of the X-ray activity, and about the same period before the maximum of the H_alpha line equivalent width (in emission) was reached at only ~ -5 \AA. In this work we found that the global correlation between the BV variability and the X-ray intensity was also observed at longer wavelengths in the IR domain.Comment: 11 pages, 7 figures, and online material (2 tables). Submitted to A&A in 2014 Januar

Severity and progression rate of periodontitis are associated with an increased risk of hypertension of patients attending the university clinic

Peer reviewe

Aggregatibacter actinomycetemcomitans Biofilm Reduces Gingival Epithelial Cell Keratin Expression in an Organotypic Gingival Tissue Culture Model

Epithelial cells express keratins, which are essential for the structural integrity and mechanical strength of the cells. In the junctional epithelium (JE) of the tooth, keratins such as K16, K18, and K19, are expressed, which is typical for non-differentiated and rapidly dividing cells. The expression of K17, K4, and K13 keratins can be induced by injury, bacterial irritation, smoking, and inflammation. In addition, these keratins can be found in the sulcular epithelium and in the JE. Our aim was to estimate the changes in K4, K13, K17, and K19 expression in gingival epithelial cells exposed to Aggregatibacter actinomycetemcomitans. An organotypic gingival mucosa and biofilm co-culture was used as a model system. The effect of the biofilm after 24 h was assessed using immunohistochemistry. The structure of the epithelium was also studied with transmission electron microscopy (TEM). The expression of K17 and K19, as well as total keratin expression, decreased in the suprabasal layers of epithelium, which were in close contact with the A. actinomycetemcomitans biofilm. The effect on keratin expression was biofilm specific. The expression of K4 and K13 was low in all of the tested conditions. When stimulated with the A. actinomycetemcomitans biofilm, the epithelial contact site displayed a thick necrotic layer on the top of the epithelium. The A. actinomycetemcomitans biofilm released vesicles, which were found in close contact with the epithelium. After A. actinomycetemcomitans irritation, gingival epithelial cells may lose their resistance and become more vulnerable to bacterial infection.</p

The Fermi –Gbm Three-Year X-Ray Burst Catalog

The Fermi Gamma Ray Burst Monitor (GBM) is an all sky gamma-ray monitor well known in the gamma-ray burst community. Although GBM excels in detecting the hard, bright extragalactic GRBs, its sensitivity above 8 keV and all-sky view make it an excellent instrument for the detection of rare, short-lived Galactic transients. In March 2010, we initiated a systematic search for transients using GBM data. We conclude this phase of the search by presenting a 3 year catalog of 1084 X-ray bursts. Using spectral analysis, location and spatial distributions we classified the 1084 events into 752 thermonuclear X-ray bursts, 267 transient events from accretion flares and X-ray pulses, and 65 untriggered gamma-ray bursts. All thermonuclear bursts have peak blackbody temperatures broadly consistent with photospheric radius expanison (PRE) bursts. We find an average rate of 1.4 PRE bursts per day, integrated over all Galactic bursters within about 10 kpc. These include 33 and 10 bursts from the ultra-compact X-ray binaries 4U~0614+09 and 2S~0918-549, respectively. We discuss these recurrence times and estimate the total mass ejected by PRE bursts in our Galaxy

Three years of Fermi GBM Earth Occultation Monitoring: Observations of Hard X-ray/Soft Gamma-Ray Sources

The Gamma ray Burst Monitor (GBM) on board Fermi has been providing continuous data to the astronomical community since 2008 August 12. In this paper we present the results of the analysis of the first three years of these continuous data using the Earth occultation technique to monitor a catalog of 209 sources. From this catalog, we detect 99 sources, including 40 low-mass X-ray binary/neutron star systems, 31 high-mass X-ray binary neutron star systems, 12 black hole binaries, 12 active galaxies, 2 other sources, plus the Crab Nebula, and the Sun. Nine of these sources are detected in the 100-300 keV band, including seven black-hole binaries, the active galaxy Cen A, and the Crab. The Crab and Cyg X-1 are also detected in the 300-500 keV band. GBM provides complementary data to other sky-monitors below 100 keV and is the only all-sky monitor above 100 keV. Up-to-date light curves for all of the catalog sources can be found at http://heastro.phys.lsu.edu/gbm/.Comment: 24 pages, 12 figures, accepted for publication in ApJ