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Multiple Mediators (multiple + mediator)
Selected AbstractsThe Complexity of Trauma Types in the Lives of Women in Families Referred for Family Violence: Multiple Mediators of Mental HealthAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 4 2008Victoria L. Banyard PhD Responding to calls for further research about the impact of multiple types of trauma across the life span, this study examines the interconnections among types of trauma in childhood and adulthood in a convenience clinical sample of 283 women obtaining social services for family violence. In particular, variables including family of-origin dysfunction and other childhood risk factors, relationship victimization in adulthood, and the presence of adult resources were examined as mediators of links between child maltreatment and adult mental health symptoms. Variables were assessed at different time points, 3 years apart. Path analysis revealed that the conceptual model of multiple pathways between childhood family violence exposure and adult outcomes fit the data well. In particular, the link between child maltreatment and adult trauma symptoms was mediated by more proximal adult sexual and intimate partner violence and its association with childhood risk markers (e.g., negative family environment) and decreased markers of resources. This link was not significant for a more general index of mental health symptoms in adulthood. [source] Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2008Akiko Nagasaka Abstract Osteopontin (OPN), originally discovered in bone as an extracellular matrix protein, was identified in many cell types in the immune system, presumably being involved in many aspects of pathogenesis of inflammatory and immune diseases. Mast cells are also involved in such pathological aspects by secreting multiple mediators. However, it has not been determined whether mast cells produce OPN and whether it affects their function. To test this, we used murine fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured mast cells. We found that OPN was spontaneously produced by FSMC and inducible by ionomycin and Fc,RI aggregation in bone marrow-derived cultured mast cells. In the presence of mast cell growth factors, FSMC were similarly generated from both OPN-deficient (OPN,/,) and -sufficient (OPN+/+) mice without significant differences in yield, purity, granularity, and viability. Using OPN,/, FSMC, we found that recombinant OPN augmented IgE-mediated degranulation and induced FSMC chemotaxis. Both effects were mediated by OPN receptors (i.e. CD44 and integrin,,v). IgE-mediated passive cutaneous anaphylaxis was significantly reduced in OPN,/, mice compared with OPN+/+ mice, indicating physiological relevance of OPN. These results indicate that OPN is a mast cell mediator, enhances mast cell responses to antigen, and thus may influence mast cell-related pathological conditions. See accompanying commentary at http://dx.doi.org/10.1002/eji200738131 [source] Activation of Protease-Activated Receptor-2 Leads to Inhibition of Osteoclast Differentiation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Rosealee Smith Abstract PAR-2 is expressed by osteoblasts and activated by proteases present during inflammation. PAR-2 activation inhibited osteoclast differentiation induced by hormones and cytokines in mouse bone marrow cultures and may protect bone from uncontrolled resorption. Introduction: Protease-activated receptor-2 (PAR-2), which is expressed by osteoblasts, is activated specifically by a small number of proteases, including mast cell tryptase and factor Xa. PAR-2 is also activated by a peptide (RAP) that corresponds to the "tethered ligand" created by cleavage of the receptor's extracellular domain. The effect of activating PAR-2 on osteoclast differentiation was investigated. Materials and Methods: Mouse bone marrow cultures have been used to investigate the effect of PAR-2 activation on osteoclast differentiation induced by parathyroid hormone (PTH), 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], and interleukin-11 (IL-11). Expression of PAR-2 by mouse bone marrow, mouse bone marrow stromal cell-enriched cultures, and the RAW264.7 osteoclastogenic cell line was demonstrated by RT-PCR. Results: RAP was shown to inhibit osteoclast differentiation induced by PTH, 1,25(OH)2D3, or IL-11. Semiquantitative RT-PCR was used to investigate expression of mediators of osteoclast differentiation induced by PTH, 1,25(OH)2D3, or IL-11 in mouse bone marrow cultures and primary calvarial osteoblast cultures treated simultaneously with RAP. In bone marrow and osteoblast cultures treated with PTH, 1,25(OH)2D3, or IL-11, RAP inhibited expression of RANKL and significantly suppressed the ratio of RANKL:osteoprotegerin expression. Activation of PAR-2 led to reduced expression of prostaglandin G/H synthase-2 in bone marrow cultures treated with PTH, 1,25(OH)2D3, or IL-11. RAP inhibited PTH- or 1,25(OH)2D3 -induced expression of IL-6 in bone marrow cultures. RAP had no effect on osteoclast differentiation in RANKL-treated RAW264.7 cells. Conclusion: These observations indicate that PAR-2 activation inhibits osteoclast differentiation by acting on cells of the osteoblast lineage to modulate multiple mediators of the effects of PTH, 1,25(OH)2D3, and IL-11. Therefore, the role of PAR-2 in bone may be to protect it from uncontrolled resorption by limiting levels of osteoclast differentiation. [source] Cytokines, matrix metalloproteases, angiogenic and growth factors in tears of normal subjects and vernal keratoconjunctivitis patientsALLERGY, Issue 5 2009A. Leonardi Background:, To detect the presence of multiple mediators and growth factors in tears of vernal keratoconjunctivitis (VKC) patients with active disease using stationary phase antibody arrays. Methods:, Tears were collected from 12 normal subjects (CT) and 24 active VKC patients. Tears were centrifuged and successively probed using three microwell plate arrays specific for: (i) cytokines: interleukin (IL)-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, interferon-, and tumour necrosis factor-,; (ii) growth factors: basic fibroblast growth factor (bFGF), platelet-derived growth factor, thrombopoietin, angiopoietin-2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), keratocyte growth factor, tissue inhibitor of metalloprotease (TIMP)-1 and heparin-binding epithelial growth factor (HB-EGF) and (iii) matrix metalloprotease (MMP)-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1 and TIMP-2. Results:, Interleukin-8 signals were detected in all CT and highly detected in all VKC samples. The Th2-type cytokines, IL-4, IL-5 and IL-10 were detected only in tears of VKC patients. Signals for bFGF, HB-EGF, VEGF and HGF were detected in 41,87% of VKC samples and in few CT samples. Only TIMP-1 and TIMP-2 were found in all normal and patient tear samples, whereas MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10 were highly present in all VKC samples. Conclusions:, Stationary phase antibody array methodology was useful for the screening of various cytokines, growth factors and MMPs in tears. These analyses identified in tears of VKC patients previously unreported factors including MMP-3 and MMP-10 and multiple proteases, growth factors and cytokines, which may all play an important role in the pathogenesis of conjunctival inflammation. [source] Does social problem solving mediate the relationship between personality traits and personality disorders?PERSONALITY AND MENTAL HEALTH, Issue 3 2010An exploratory study with a sample of male prisoners Background Social problem solving therapy is one helpful approach to treating people with personality disorders (PD). Consequently, it is worthwhile to develop a greater understanding of the role of social problem solving in PD. One hypothesis is that social problem solving mediates the relationship between personality dimensions and personality disorder. This premise was explored in a sample of male prisoners, a population known to have a high prevalence of PD. Method Sixty-eight men completed the International Personality Disorder Examination (IPDE), NEO-Five Factor Inventory (NEO-FFI) and the Social Problem-Solving Inventory,Revised: Short Version (SPSI-R:S). The data were explored for direct and indirect mediational effects of social problem solving variables in the personality dimension,PD relationship, using methods appropriate for small samples and multiple mediators. Results A number of relationships between personality dimensions, social problem solving, and personality disorder traits were identified, but only for paranoid, schizotypal, borderline, narcissistic, and avoidant PDs. Discussion These findings support the hypothesis that social problem solving mediates between personality dimensions and some PDs. Further research is necessary to verify these relationships. However, these findings begin to clarify the mechanisms by which personality dimensions relate to PDs. This knowledge has potential to contribute to the development of more effective interventions for people with particular personality dimensions and specific personality disorders. Copyright © 2010 John Wiley & Sons, Ltd. [source] Role of Complement Anaphylatoxin C3a in Photodynamic Therapy-elicited Engagement of Host Neutrophils and Other Immune CellsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006Ivana Cecic ABSTRACT Tumor treatment by photodynamic therapy (PDT) provokes a host-protective inflammatory and acute-phase response and an immune reaction. Neutrophilia manifested in this context is driven by multiple mediators of neutrophil chemotaxis orchestrated by an activated complement system. Mouse FsaR fibrosarcoma was used in this study to further investigate neutrophilia induced by Photofrin-based PDT. The complement anaphylatoxin C3a was identified as a major chemo-attractant in the advanced phase of PDT-induced neutrophilia, because injecting mice with antibodies blocking its receptor C3aR significantly inhibited the increase in neutrophil levels 8 h after PDT. At the same time point, an increased C3aR expression was detected in neutrophils, monocytes and B lymphocytes in the blood of host mice. Peritoneal macro-phages and mast cells harvested from treatment-naive mice exhibited elevated C3aR expression after coincubation in vitro for 8 h with PDT-treated FsaR cells. Thus, C3a emerges as one of the key effector molecules engaged in PDT-induced host response. [source] | ||||||||||