The influence of inflammatory cytokines in physiopathology of suicidal behavior.

BACKGROUND: Based on the urgent need for reliable biomarkers in relation to suicide risk both for more accurate prediction as well as for new therapeutic opportunities, several researchers have been studied evidences of the potential participation of inflammatory processes in the brain, in particular cytokines, in suicide. The purpose of this review was to analyze the associations between inflammation markers and suicide. METHODS: To achieve this goal, a systematic review of literature was conducted via electronic database Scopus using the Medical Subject Headings (MeSH) terms: "cytokines", "suicide" and "inflammation". Through this search it was found 54 articles. After analyzing them 15 met the eligibility criteria and were included in the final sample. RESULTS: One of the most mentioned inflammatory markers was Interferon-α (IFN-α), a pro-inflammatory cytokine which has been shown to increase serum concentrations of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-a (TNF- α) and IFN-ϒ, which are factors increased suicide victims and attempters. In this line, IL-6 is not only found to be elevated in the cerebrospinal fluid of suicide attempters, even its levels in the peripheral blood have been proposed as a biological suicide marker. Another study stated that increased levels of IL-4 and IL-13 transcription in the orbitofrontal cortex of suicides suggest that these cytokines may affect neurobehavioral processes relevant to suicide. LIMITATIONS: A lack of studies and great amount of cross-sectional studies. CONCLUSION: Inflammation may play an important role in the pathophysiology of suicide, especially, levels of some specific inflammatory cytokines.

Concomitant multipotent and unipotent dental pulp progenitors and their respective contribution to mineralised tissue formation.

Upon in vitro induction or in vivo implantation, the stem cells of the dental pulp display hallmarks of odontoblastic, osteogenic, adipogenic or neuronal cells. However, whether these phenotypes result from genuine multipotent cells or from coexistence of distinct progenitors is still an open question. Furthermore, determining whether a single cell-derived progenitor is capable of undergoing a differentiation cascade leading to tissue repair in situ is important for the development of cell therapy strategies. Three clonal pulp precursor cell lines (A4, C5, H8), established from embryonic ED18 first molars of mouse transgenic for a recombinant plasmid adeno-SV40, were induced to differentiate towards the odonto/osteogenic, chondrogenic or adipogenic programme. Expression of phenotypic markers of each lineage was evaluated by RT-PCR, histochemistry or immunocytochemistry. The clones were implanted into mandibular incisors or calvaria of adult mice. The A4 clone was capable of being recruited towards at least 3 mesodermal lineages in vitro and of contributing to dentin-like or bone formation, in vivo, thus behaving as a multipotent cell. In contrast, the C5 and H8 clones displayed a more restricted potential. Flow cytometric analysis revealed that isolated monopotent and multipotent clones could be distinguished by a differential expression of CD90. Altogether, isolation of these clonal lines allowed demonstrating the coexistence of multipotential and restricted-lineage progenitors in the mouse pulp. These cells may further permit unravelling specificities of the different types of pulp progenitors, hence facilitating the development of cell-based therapies of the dental pulp or other cranio-facial tissues.

Amelogenin gene splice products A+4 and A-4 implanted in soft tissue determine the reorientation of CD45-positive cells to an osteo-chondrogenic lineage.

Several molecules such as bone morphogenetic protein-7, bone sialoprotein (BSP), or amelogenin gene splice products (A+4 or A-4) have been shown to induce reparative dentin formation in a rat model. However, at the moment, the origin and the mechanism of differentiation of the pulp cells stimulated by the bioactive molecules remain poorly understood. The present investigation was undertaken to validate an ectopic oral mucosal mouse model to evaluate the effects of amelogenin gene splice product implantation in a non-mineralizing tissue. Agarose beads, alone or coated with amelogenin gene splice products, were implanted in the mucosa of the cheeks in mouse. An immunohistochemical characterization of the recruited cells was undertaken for 3 days, 8 days, and 30 days after the implantation. The results showed that the implantation of agarose beads in mucosa induced the recruitment of inflammatory CD45 positive cells. When the beads were coated with amelogenin gene splice products (A+4 or A-4), the expression of osteo-chondrogenic markers (RP59, Sox9, or BSP) was also observed. However, no mineralization nodule was observed, even after 30 days of implantation. The present investigation suggests that amelognin gene splice products have the capacity of recruiting among inflammatory cell mesenchymal progenitors that eventually differentiate into osteo-chondrogenic cells. Altogether, the results obtained in the pulp model and the present data suggest the existence of different pathways of cell recruitment and differentiation in different cellular environments.