CD93 is a cell surface lectin receptor involved in the control of the inflammatory response stimulated by exogenous DNA

Bacterial DNA contains CpG oligonucleotide (ODN) motifs to trigger innate immune responses through the endosomal receptor Toll-like receptor 9 (TLR9). One of the cell surface receptors to capture and deliver microbial DNA to intracellular TLR9 is the C-type lectin molecule DEC-205 through its N-terminal C-type lectin-like domain (CTLD). CD93 is a cell surface protein and member of the lectin group XIV with a CTLD. We hypothesized that CD93 could interact with CpG motifs, and possibly serve as a novel receptor to deliver bacterial DNA to endosomal TLR9. Using ELISA and tryptophan fluorescence binding studies we observed that the soluble histidine-tagged CD93-CTLD was specifically binding to CpG ODN and bacterial DNA. Moreover, we found that CpG ODN could bind to CD93-expressing IMR32 neuroblastoma cells and induced more robust interleukin-6 secretion when compared with mock-transfected IMR32 control cells. Our data argue for a possible contribution of CD93 to control cell responsiveness to bacterial DNA in a manner reminiscent of DEC-205. We postulate that CD93 may act as a receptor at plasma membrane for DNA or CpG ODN and to grant delivery to endosomal TLR9.     

The association between wear facets,bruxism, and severity of facial pain in patients with temporomandibular disorders

STATEMENT OF PROBLEM: It is unclear whether patients with temporomandibular disorders (TMD) who report high levels of bruxism have more severe signs and symptoms of TMD and more advanced tooth wear than patients with TMD who report lower levels of bruxism. PURPOSE: The purpose of this study was to determine whether there was a significant association between tooth wear, the parafunctional oral habit of bruxism, temporomandibular joint (TMJ) pain, and muscle pain severity in a TMD population. MATERIAL AND METHODS: A total of 84 subjects previously diagnosed with TMD, according to the Research Diagnostic Criteria for TMD (RDC/TMD) and who met 10 specific inclusion/exclusion criteria underwent a thorough multiaxial examination and classification recommended by the National Institute of Dental and Craniofacial Research (NIDCR). Measurement of tooth wear facets by use of a 4-point scale were graded in 10 zones on mandibular casts. One calibrated examiner performed all scoring. Bruxism was assessed in a standardized pretreatment questionnaire and in the dental history and interview (RDC/TMD) to indicate how frequently (0 = never to 3 = very often) subjects performed a list of oral habits, which included bruxism. The Kappa reliability coefficient (range from: -1.0 to 1.0) was used to correct for chance agreement, and was computed for each of the 10 study sites designated for rating. Subjects were also compared for muscle and joint pain. Muscle pain was a summed measure derived from the dental examination findings (range 0 to 20), calculated from the presence or absence of pain induced by palpation of 20 predetermined muscle sites. Similarly, joint pain was a summed measure of the presence or absence of pain in the TMJs induced by palpation of the joints on the outer surface and in the external auditory canal in 5 different positions of the mandible. A Pearson product-moment correlation was used to compute the summed severity of tooth wear and the subjects' age. Analysis of covariance was used to determine whether the number of wear facets was significantly higher in patients with TMD who reported a history of bruxism, compared with patients with TMD who reported no or minimal bruxism, after controlling for the effect of age. Multivariate analysis of variance was used to determine whether the number of painful muscles of mastication and joint sites on standardized examination were significantly higher in patients with TMD with a history of bruxism (alpha=.05). RESULTS: In the population tested, tooth wear was modestly correlated with age (r =.40, P<.001). Of the 84 subjects studied, 11.9% reported no bruxing activity, 32.1% reported some or occasional bruxing activity, and 47.6% had frequent bruxism activity; the remaining 8.4% were eliminated from analysis because they provided inconsistent responses. Bruxism activity was not correlated with muscle pain on palpation and was inversely associated with TMJ pain on palpation. Tooth wear was not significantly correlated with bruxism, TMJ pain, or muscle pain. CONCLUSIONS: In this TMD population, tooth wear factors did not differentiate patients with bruxism from those without. The amount of bruxism activity was not associated with more severe muscle pain and was associated with less pain in the TMJ on palpation.     

Mls-1-like superantigen in the MA/MyJ mouse is encoded by a new mammary tumor provirus that is distinct from Mtv-7

Mls-1 is an endogenous superantigen that leads to in vivo deletion and in vitro stimulation of T cell receptor (TCR) V beta 6-, 7-, 8.1-, and 9-expressing cells. The MA/MyJ mouse deletes the identical set of TCR from its mature T cell repertoire; however, it does not contain Mtv-7, the murine mammary tumor provirus (MMTV), whose sag gene encodes Mls-1. Interestingly, the superantigen activity of this mouse strain segregates with a new mammary tumor provirus, Mtv-43, not seen in other inbred strains. The predicted amino acid sequence of the sag gene of Mtv-43 was compared with that of Mtv-7. Strikingly, the COOH terminus of the two molecules is very similar, while all other MMTV-encoded superantigens differ 100% in this segment.     

Angiotensin and mineralocorticoid receptor antagonism attenuates cardiac oxidative stress in angiotensin II‐infused rats

Angiotensin II (Ang II) and aldosterone contribute to hypertension, oxidative stress and cardiovascular damage, but the contributions of aldosterone during Ang II‐dependent hypertension are not well defined because of the difficulty to assess each independently. To test the hypothesis that during Ang II infusion, oxidative and nitrosative damage is mediated through both the mineralocorticoid receptor (MR) and angiotensin type 1 receptor (AT1), five groups of Sprague–Dawley rats were studied: (i) control; (ii) Ang II infused (80 ng/min × 28 days); (iii) Ang II + AT1 receptor blocker (ARB; 10 mg losartan/kg per day × 21 days); (iv) Ang II + mineralocorticoid receptor (MR) antagonist (Epl; 100 mg eplerenone/day × 21 days); and (v) Ang II + ARB + Epl (Combo; × 21 days). Both ARB and combination treatments completely alleviated the Ang II‐induced hypertension, whereas eplerenone treatment only prolonged the onset of the hypertension. Eplerenone treatment exacerbated the Ang II‐mediated increase in plasma and heart aldosterone 2.3‐ and 1.8‐fold, respectively, while ARB treatment reduced both. Chronic MR blockade was sufficient to ameliorate the AT1‐mediated increase in oxidative damage. All treatments normalized protein oxidation (nitrotyrosine) levels; however, only ARB and Combo treatments completely reduced lipid peroxidation (4‐hydroxynonenal) to control levels. Collectively, these data suggest that receptor signalling, and not the elevated arterial blood pressure, is the principal culprit in the oxidative stress‐associated cardiovascular damage in Ang II‐dependent hypertension.