Regulation of MMP-3 expression and secretion by the chemokine eotaxin-1 in human chondrocytes

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is characterized by the degradation of articular cartilage, marked by the breakdown of matrix proteins. Studies demonstrated the involvement of chemokines in this process, and some may potentially serve as diagnostic markers and therapeutic targets; however, the underlying signal transductions are not well understood.</p> <p>Methods</p> <p>We investigated the effects of the CC chemokine eotaxin-1 (CCL11) on the matrix metalloproteinase (MMP) expression and secretion in the human chondrocyte cell line SW1353 and primary chondrocytes.</p> <p>Results</p> <p>Eotaxin-1 significantly induced MMP-3 mRNA expression in a dose-dependent manner. Inhibitors of extracellular signal-regulated kinase (ERK) and p38 kinase were able to repress eotaxin-1-induced MMP-3 expression. On the contrary, Rp-adenosine-3',5'-cyclic monophosphorothioate (Rp-cAMPs), a competitive cAMP antagonist for cAMP receptors, and H-89, a protein kinase A (PKA) inhibitor, markedly enhanced eotaxin-1-induced MMP-3 expression. These results suggest that MMP-3 expression is specifically mediated by the G protein-coupled eotaxin-1 receptor activities. Interestingly, little amount of MMP-3 protein was detected in the cell lysates of eotaxin-1-treated SW1353 cells, and most of MMP-3 protein was in the culture media. Furthermore we found that the eotaxin-1-dependent MMP-3 protein secretion was regulated by phospholipase C (PLC)-protein kinase C (PKC) cascade and c-Jun N-terminal kinase (JNK)/mitogen-activated protein (MAP) kinase pathways. These data indicate a specific regulation of MMP-3 secretion also by eotaxin-1 receptor activities.</p> <p>Conclusions</p> <p>Eotaxin-1 not only induces MMP-3 gene expression but also promotes MMP-3 protein secretion through G protein-coupled eotaxin-1 receptor activities. Chemokines, such as eotaxin-1, could be a potential candidate in the diagnosis and treatment of arthritis.</p

Spirituality and/or religious faith: A means for coping with the effects of amyotrophic lateral sclerosis/motor neuron disease?

OBJECTIVE: The notion of spirituality/religious belief is recognized internationally as a domain within end-of-life care and is important in patients' and carers' quality-of-life. When faced with incurable illness, patients often become more philosophical about their life; many seek comfort in spiritual or religious philosophies. Our intention was to understand how personal spirituality and religious faith might help those living with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) cope with their impending death. METHOD: Unsolicited narratives (internet and print-published) written by individuals diagnosed with the terminal condition of ALS/MND were analyzed thematically. Narratives from 161 individuals diagnosed with ALS/MND written over a period of 37 years (from 1968 to 2005) were included. RESULTS: Our findings reveal that religious faith sustains and helps people to avoid despair, and personal spirituality helps them make sense of what is happening to them. SIGNIFICANCE OF RESULTS: The use of personal narratives by people with ALS/MND has provided a vehicle for sharing their deepest spiritual and religious thoughts with others. The place of spirituality and religious faith within ALS/MND care should not be underestimated. Assessment of religious or spiritual needs should become a routine part of practice and is the responsibility of all members of the multidisciplinary team