RESUMEN
BACKGROUND: Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. RESULTS: PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. CONCLUSIONS: PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease.
Asunto(s)
Enfermedades de los Perros/patología , Mediadores de Inflamación/sangre , Degeneración del Disco Intervertebral/veterinaria , Desplazamiento del Disco Intervertebral/veterinaria , Animales , Ciclooxigenasa 2/biosíntesis , Enfermedades de los Perros/sangre , Perros , Matriz Extracelular/metabolismo , Degeneración del Disco Intervertebral/sangre , Degeneración del Disco Intervertebral/patología , Desplazamiento del Disco Intervertebral/sangre , Desplazamiento del Disco Intervertebral/patología , Osteocondrodisplasias/patología , Osteocondrodisplasias/veterinariaRESUMEN
Integrin beta 4, one of the heterodimeric receptors, is expressed predominantly on epithelial cells. It is concentrated at the basement membrane zone, where it localizes to specialized adhesion structures called hemidesmosomes. In addition to its adhesive functions, novel insights have emerged regarding the specific roles of integrin beta 4 in their attachment to extracellular matrix and in their signal transduction pathways within the central nervous system (CNS) and peripheral nervous system in the past few years. It has been reported that integrin beta 4 is expressed in several kinds of neural cells including astrocyte, Schwann cells, neurons, and neural stem cells. In the mean while, it is expressed by some Schwann cells in the peripheral nervous system and mediated the Mycobacterium leprae invade the peripheral nervous system to reach the Schwann cells. This review highlights recent progress in the function and regulation of integrin beta 4 in neural cells.
Asunto(s)
Integrina beta4/metabolismo , Sistema Nervioso/metabolismo , Neuronas/metabolismo , Animales , Astrocitos/citología , Astrocitos/metabolismo , Adhesión Celular/fisiología , Matriz Extracelular/metabolismo , Hemidesmosomas/metabolismo , Humanos , Sistema Nervioso/citología , Neuronas/citología , Células de Schwann/citología , Células de Schwann/metabolismo , Células de Schwann/microbiología , Células Madre/citología , Células Madre/metabolismoRESUMEN
Dystroglycan connects the extracellular matrix and cytoskeleton. Key findings in the past year indicate that dystroglycan interacts with a wider repertoire of extracellular ligands than originally appreciated, that dystroglycan plays a critical role in organizing extracellular matrix molecules on the cell surface and in basement membranes, and that at least two human pathogens utilize dystroglycan to gain access to host cells. Together, these advances begin to help elucidate important biological roles for dystroglycan in development and disease.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Proteínas del Citoesqueleto/fisiología , Glicoproteínas de Membrana/fisiología , Animales , Adhesión Bacteriana , Moléculas de Adhesión Celular/fisiología , Proteínas del Citoesqueleto/química , Citoesqueleto/metabolismo , Distroglicanos , Matriz Extracelular/metabolismo , Quinasa 1 de Adhesión Focal , Proteína-Tirosina Quinasas de Adhesión Focal , Proteína Adaptadora GRB2 , Humanos , Laminina/metabolismo , Ligandos , Glicoproteínas de Membrana/química , Proteínas Musculares/fisiología , Distrofias Musculares/metabolismo , Mycobacterium leprae/metabolismo , Unión Proteica , Proteínas Tirosina Quinasas/fisiología , Proteínas/fisiología , Dominios Homologos srcRESUMEN
Fibroblasts and a host of macrophage secretory products have been implicated in a number of diseases where excess extracellular matrix (ECM) deposition is the main pathological feature. Fibrosis characterized by excessive deposition of collagen also contributes to the irreversible nerve damage observed in leprosy. Since M. leprae are seen within neurofibroblasts (Nf) in the advanced stages of the disease and macrophages form a common infiltrating cellular constituent of leprous nerves at all stages, secretion of ECM proteins by Nf was studied, in vitro following infection with M. leprae and in the presence of macrophage secretory products. These studies were compared in cells derived from two strains of mice, Swiss White (SW) and C57BL/6, as they differ in their response to M. leprae infection and parallel those observed in lepromatous and tuberculoid patients, respectively. On infection with M. leprae, Nfs showed a decrease in secretion of collagen type IV in SW and type I in C57Bl/6 strain. Macrophages caused a further decrease in the secretion of collagen types affected by M. leprae infection per se, while the other collagen types, viz. I and III in SW strain and III and IV in C57Bl/s strain, were unaffected. This study indicates that neural collagenization in nerves in advanced leprosy may be of Nf origin. However, unlike other diseases with excess collagen deposition, ECM proteins produced by Nfs in response to nerve damage may not be of prime importance in the progression of leprous neuropathy and occur as a general response to loss of cellular content in leprous nerves.