Coupled cell networks of astrocytes and chondrocytes are target cells of inflammation

Abstract

Abstract Aims Systemic low-grade inflammation can be initiated in vivo after traumatic injury or in chronic diseases as neurodegenerative, metabolic and autoimmune diseases. Coupled cell networks are target cells leading to the spread of inflammation and changes in biochemical cellular parameters. Do astrocytes and chondrocytes behave in a similar way in an inflammatory reactive state with respect to Ca2+ signaling, actin filaments rearrangement, receptor properties, pro-inflammatory cytokine release etc? Methods Primary cultures of astrocytes and chondrocytes, respectively, were incubated with lipopolysaccharide (LPS) (10 ng/ml, 24h) or interleukin-1β (IL-1β) (5ng/ml, 24 h) to induce inflammatory reactivity. Ca2+ signaling, Na+/K+-ATPase-, connexin 43 (Cx43)-, and Toll-like receptor 4 (TLR4)- expressions, actin filament organization, and IL-1β release were analyzed. Results Stimulation with IL-1β or LPS altered the Ca2+ signaling from single peaks to oscillating waves and increased the expression of Cx43 and TLR4, and decreased expression of Na+/K+-ATPase. A disruption of the actin filaments with more pronounced ring-formed structures was found in inflammatory induced astrocytes and chondrocytes which in turn affects Ca2+ oscillations. Additionally a release of active matrix metallopeptidase-13 was found in media from IL-1β stimulated chondrocytes. Conclusions Our data show that cellular mechanisms of healthy chondrocytes as well as inflamed, resemble the coupled cell networks of astrocytes. Chronic, low-grade inflammation can influence coupled cell networks in one or several organs, leading to co-morbidity. It is crucial that inflammatory affected cells in various organs are restored back to a physiological non-inflammatory homeostasis in order to prevent tissue degradation and pain.