Differential expression and potential role of SOCS1 and SOCS3 in Wallerian degeneration in injured peripheral nerve.
Pro-inflammatory chemokines and cytokines play an important role in Wallerian degeneration (WD) after peripheral nerve injury. These pro-inflammatory signals are "turned-off" in a timely manner to ensure that the inflammatory response in the injured nerve is limited. The factors that regulate the turning-off of the pro-inflammatory state are not fully understood. The suppressors of cytokine signaling (SOCS) proteins are potential candidates that could limit the inflammatory response by acting to regulate cytokine signaling at the intracellular level. In this work we show that the expression SOCS1 and SOCS3 proteins differ from each other during WD in the mouse sciatic nerve after cut/ligation and crush injuries. SOCS1 is mainly expressed by macrophages and its expression is inversely correlated with phosphorylation of JAK2 and STAT3 signaling proteins and the expression of pro-inflammatory cytokines IL-1beta and TNFalpha. In addition, treatment of cut/ligated nerves, which express lower levels of SOCS1 as compared to crush injury, with a SOCS1 mimetic peptide leads to a decrease in macrophage numbers at 14 days post-injury and reduces IL-1beta mRNA expression 1 day post-injury. In contrast, SOCS3 expression is restricted mainly to Schwann cells and is negatively correlated with the expression of IL-6 and LIF. These data suggest that SOCS1 and SOCS3 may play different roles in WD and provide a better understanding of some of the potential regulatory mechanisms that may control inflammation and regeneration in the injured peripheral nerve.
Girolami
Elizabeth I
EI
Centre for Research in Neuroscience, The Research Institute of the McGill University Health Centre, Livingston Hall, Room L7-210, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4.
Bouhy
Delphine
D
Haber
Michael
M
Johnson
Howard
H
David
Samuel
S
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000150:complications*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
D000943:Antigens, Differentiation; D016207:Cytokines; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C036763:monocyte-macrophage differentiation antigen; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2