International Immunology, Vol. 12, No. 9, 1329-1335,
September 2000
© 2000 Japanese Society for Immunology
Cytokines and chemokines are both expressed by human myoblasts: possible relevance for the immune pathogenesis of muscle inflammation.
Laboratory of Neuroimmunology, Department of Neuromuscular Diseases, National Neurological Institute `Carlo Besta', 20133 Milan, Italy
1 Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304-1104, USA
Correspondence to: M. De Rossi
The idiopathic inflammatory myopathies are characterized by antibody- or cell-mediated immune response against unknown muscle tissue antigens. In these diseases a cellular infiltrate, composed of T and B lymphocytes, macrophages and NK cells, may invade muscle tissue with a gradient from the perivascular space to the endomysial compartment. Muscle cells may be actively involved in the processes of mononuclear cell recruitment and activation from the blood stream to the areas of inflammation. In order to verify this hypothesis, cultured human myoblasts were tested for their capacity to express different pro-inflammatory cytokines [IL-1
, IL-1ß, IL-6 and tumor necrosis factor (TNF)-] and chemokines (IL-8, MCP-1 and RANTES) at the mRNA level and protein secretion, in the presence of the pro-inflammatory cytokines IFN-
and TNF- alone or in combination. We confirmed that human myoblasts expressed IL-1 and IL-6 constitutively, while IL-1ß and TNF- are detected only after treatment with pro-inflammatory cytokines; moreover, we observed that TNF- was expressed on an autocrine fashion by myoblasts. IL-8 and RANTES were expressed constitutively while MCP-1 after proper induction. These molecular data were further confirmed by specific ELISA in the supernatant from cultured myoblasts. Our results underline the importance of human myoblasts in the recruitment of leukocytes from the blood stream and, most probably, in the cross-talk between infiltrating inflammatory cells and muscle cells, creating the conditions for a chronic inflammation. Moreover, the capacity of muscle cells to behave as cells of the immune system has to be kept in mind, also in view of i.m. vaccination and use of molecular engineered myoblasts as vehicles in gene therapy.
Keywords: chemokines, cytokines, human myoblasts, idiopathic inflammatory myopathies
Transmitting editor: L. Steinman
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