Oncostatin M expression is functionally connected to neutrophils in the early inflammatory phase of skin repair: implications for normal and diabetes-impaired wounds.
In this study, we investigated the role of the cytokine oncostatin M (OSM) for wound biology. OSM and its specific OSM receptor subunit beta (OSMRbeta) were induced upon injury. OSM induction paralleled the early influx of polymorphonuclear neutrophils (PMN) into the wound. OSM protein was localized in PMN in very early wounds, whereas OSMRbeta could be detected on macrophages, keratinocytes, and fibroblasts later in repair. To establish a functional connection between PMN and OSM expression in wounds, we depleted mice from circulating PMN by injecting an anti-PMN monoclonal antibody (Ly-6G). PMN-depleted wounds were characterized by a nearly complete loss of OSM but not OSMRbeta mRNA and protein expression within the initial 16-24 hours after injury. PMN-rich chronic wounds from diabetic ob/ob mice were characterized by a strongly elevated OSM mRNA and protein expression as compared to healthy animals. Moreover, a leptin-mediated improvement of chronic wounds in ob/ob mice was paralleled by a complete inhibition of PMN influx associated again with a dramatic loss of OSM expression at the wound site. These data constitute strong evidence that OSM expression during wound inflammation is functionally connected to PMN infiltration.
Goren
Itamar
I
pharmazentrum frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Kämpfer
Heiko
H
Müller
Elke
E
Schiefelbein
Dana
D
Pfeilschifter
Josef
J
Frank
Stefan
S
D000818:Animals; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005260:Female; D007249:Inflammation / Q000503:physiopathology*; D007375:Interleukin-1 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D053683:Oncostatin M; D018121:Receptors, Cytokine / Q000032:analysis / Q000235:genetics; D053677:Receptors, Oncostatin M; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014945:Wound Healing / Q000502:physiology*
D016207:Cytokines; D007375:Interleukin-1; C508352:Osm protein, mouse; D018121:Receptors, Cytokine; D053677:Receptors, Oncostatin M; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M