Sepsis-induced SOCS-3 expression is immunologically restricted to phagocytes.
We have shown that immune cells from septic mice exhibit a suppressed response to exogenous stimuli in vitro. The suppressors of the cytokine signaling (SOCS) family are proteins that block intracellular signaling and can be induced by inflammatory mediators. Therefore, we hypothesized that SOCS-3 is up-regulated in immune cells in response to a septic challenge induced by cecal ligation and puncture (CLP). Mice were subjected to CLP or sham-CLP, and 2-48 h later, the blood, thymus, spleen, lung, and peritoneal leukocytes were harvested and examined. SOCS-3 was undetectable in thymocytes or blood leukocytes. In contrast, SOCS-3 was up-regulated in the spleen, lung, and peritoneal leukocytes in a time-dependent manner. Further examination revealed that only the macrophages and neutrophils expressed SOCS-3. These data suggest that cytokines and bacterial toxins present during sepsis have the ability to suppress the cytokine and/or lipopolysaccharide response and the function of immune cells by up-regulating SOCS-3.
Grutkoski
P S
PS
Division of Surgical Research, Rhode Island Hospital, Brown University Medical School, Providence, RI 02903, USA.
Chen
Y
Y
Chung
C S
CS
Ayala
A
A
D000818:Animals; D002432:Cecum / Q000293:injuries; D002460:Cell Line; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology; D008168:Lung / Q000378:metabolism; D008264:Macrophages; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D010586:Phagocytes / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D012016:Reference Values; D012097:Repressor Proteins; D018805:Sepsis / Q000503:physiopathology*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D018909:src Homology Domains
D011506:Proteins; D012097:Repressor Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors