Cytokines and chemokines as regulators of skeletal muscle inflammation: presenting the case of Duchenne muscular dystrophy

Duchenne muscular dystrophy is a severe inherited muscle disease that affects 1 in 3500 boys worldwide. Infiltration of skeletal muscle by inflammatory cells is an important facet of disease pathophysiology and is strongly associated with disease severity in the individual patient. In the chronic inflammation that characterizes Duchenne muscle, cytokines and chemokines are considered essential activators and recruiters of inflammatory cells. In addition, they provide potential beneficiary effects on muscle fiber damage control and tissue regeneration. In this review, current knowledge of cytokine and chemokine expression in Duchenne muscular dystrophy and its relevant animal disease models is listed, and implications for future therapeutic avenues are discussed

Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells

Current systems for conditional gene deletion within mouse macrophage lineages are limited by ectopic activity or low efficiency. In this study, we generated a Mafb-driven Cre strain to determine whether any dendritic cells (DCs) identified by Zbtb46-GFP expression originate from a Mafb-expressing population. Lineage tracing distinguished macrophages from classical DCs, neutrophils, and B cells in all organs examined. At steady state, Langerhans cells (LCs) were lineage traced but also expressed Zbtb46-GFP, a phenotype not observed in any other population. After exposure to house dust mite antigen, Zbtb46-negative CD64(+) inflammatory cells infiltrating the lung were substantially lineage traced, but Zbtb46-positive CD64(−) cells were not. These results provide new evidence for the unique identity of LCs and challenge the notion that some inflammatory cells are a population of monocyte-derived DCs

Consequences of cystic fibrosis transmembrane regulator mutations on inflammatory cells

Recent studies in cystic fibrosis (CF) transmembrane regulator (CFTR) mutations and function have shed light on its involvement in disease progression. The extent of cell and tissue distribution of CFTR facilitates systemic dysfunction of ion transport in patients carrying a mutation in CFTR, however, its incidences as cofounding risk factor to develop other diseases is not well studied. In this review we differentiate the dysfunctions driven by CFTR mutations in cell of the immune system and their role in CF progression and examine the types of medical treatments available to patients up to date.Fil: Grumelli, Sandra. Universidad Católica de Córdoba; ArgentinaFil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentin

Src as the link between inflammation and cancer.

Although a causal link between chronic inflammation and cancer has been established, the exact molecular mechanism linking inflammation to cancer remains largely unknown. It was previously postulated that molecular switches responsible for cancer cell development, and for infiltration of inflammatory cells into cancer, were divided into a distinct set of intracellular proteins and signaling pathways. However, recent evidence suggests that both tumor cells and tumor-infiltrating immune cells utilize the same kinases, mostly that of Src family, to facilitate cancer development and progression. In the past few years several groups have found that Src activation both in cancer and inflammatory cells is mainly driven by pro-inflammatory cytokines within the tumor microenvironment. Here we evaluate the cross talks between Src kinase pathways in immune cells and cancer cells. We conclude that Src might serve as a critical mechanistic link between inflammation and cancer, mediating and propagating a cycle between immune and tissue cells that can ultimately lead to the development and progression of cancer

Differential dependencies of monocytes and neutrophils on dectin-1, dectin-2 and complement for the recognition of fungal particles in inflammation

Peer reviewedPublisher PD

Structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 Acta Materialia Inc.The aim of this study was to investigate an in vivo tissue response to a biodegradable polyesterurethane, specifically the cellular and angiogenic response evoked by varying implant architectures in a subcutaneous rabbit implant model. A synthetic biodegradable polyesterurethane was synthesized and processed into three different configurations: a non-porous film, a porous mesh and a porous membrane. Glutaraldehyde cross-linked bovine pericardium was used as a control. Sterile polyesterurethane and control samples were implanted subcutaneously in six rabbits (n = 12). The rabbits were killed at 21 and 63 days and the implant sites were sectioned and histologically stained using haemotoxylin and eosin (H&E), Masson’s trichrome, picosirius red and immunostain CD31. The tissue–implant interface thickness was measured from the H&E slides. Stereological techniques were used to quantify the tissue reaction at each time point that included volume fraction of inflammatory cells, fibroblasts, fibrocytes, collagen and the degree of vascularization. Stereological analysis inferred that porous scaffolds with regular topography are better tolerated in vivo compared to non-porous scaffolds, while increasing scaffold porosity promotes angiogenesis and cellular infiltration. The results suggest that this biodegradable polyesterurethane is better tolerated in vivo than the control and that structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture.Irish Research Council for Science, Engineering and Technology: funded by the National Development Plan. Enterprise Ireland: Research Innovation Partnership