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Inflammatory response in human skeletal muscle cells: CXCL10 as a potential therapeutic target.
- Source :
-
European journal of cell biology [Eur J Cell Biol] 2012 Feb; Vol. 91 (2), pp. 139-49. Date of Electronic Publication: 2011 Dec 15. - Publication Year :
- 2012
-
Abstract
- Inflammatory myopathies (IMs) are systemic diseases characterized by a T helper (Th) 1 type inflammatory response and cell infiltrates within skeletal muscles. The mainstay of treatment is drugs aimed at suppressing the immune system - corticosteroids and immunosuppressants. About 25% of patients are non-responders. Skeletal muscle cells seem actively involved in the immune-inflammatory response and not only a target; understanding the molecular bases of IMs might help drug development strategies. Within muscles the interaction between the chemokine interferon (IFN)γ inducible 10 kDa protein, CXCL10 or IP-10, and its specific receptor CXCR3, present on Th1 type infiltrating cells, likely plays a pivotal role, potentially offering the opportunity for therapeutic intervention. We aimed to clarify the involvement of human skeletal muscle cells in inflammatory processes in terms of CXCL10 secretion, to elucidate the engaged molecular mechanism(s) and, finally, to evaluate muscular cell responses, if any, to some immunosuppressants routinely used in IM treatment, such as methylprednisolone, methotrexate, cyclosporin A and Infliximab. We first isolated and characterized human fetal skeletal muscle cells (Hfsmc), which expressed the specific lineage markers and showed the competence to react in the context of an in vitro alloresponse. CXCL10 protein secretion by Hfsmc was similarly induced by the inflammatory cytokines interferon (IFN)γ and tumor necrosis factor (TNF)α, above undetectable control levels, through the activation of Stat1 and NF-kB pathways, respectively; CXCL10 secretion was significantly magnified by cytokine combination, and this synergy was associated to a significant up-regulation of TNFαRII; cytokine-induced CXCL10 secretion was considerably affected only by Infliximab. Our data suggested that human skeletal muscle cells might actively self-promote muscular inflammation by eliciting CXCL10 secretion, which is known to amplify Th1 cell tissue infiltration in vivo. In conclusion, we sustain that pharmacological targeting of CXCL10 within muscular cells might contribute to keep in control pro-Th1 polarization of the immune/inflammatory response.<br /> (Copyright © 2011 Elsevier GmbH. All rights reserved.)
- Subjects :
- Antibodies, Monoclonal pharmacology
Cells, Cultured
Chemokine CXCL10 immunology
Cyclosporine pharmacology
Fetus
Humans
Immunosuppressive Agents pharmacology
Infliximab
Interferon-gamma pharmacology
Lymphocyte Activation
Methylprednisolone pharmacology
Muscle Cells drug effects
Muscle Cells immunology
Muscle, Skeletal drug effects
Muscle, Skeletal immunology
Myositis immunology
NF-kappa B metabolism
Receptors, CXCR3 immunology
STAT1 Transcription Factor metabolism
Signal Transduction
Th1 Cells immunology
Tumor Necrosis Factor-alpha pharmacology
Chemokine CXCL10 metabolism
Muscle Cells metabolism
Muscle, Skeletal metabolism
Myositis metabolism
Receptors, CXCR3 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1618-1298
- Volume :
- 91
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 22176919
- Full Text :
- https://doi.org/10.1016/j.ejcb.2011.09.011