Decreased IL-10 expression in stefin B-deficient macrophages is regulated by the MAP kinase and STAT-3 signaling pathways.
Innate immune responses are tightly regulated to avoid excessive activation and subsequent inflammatory damage to the host, and interleukin-10 (IL-10) plays a crucial role in preventing inflammation. Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases. In stefin B-deficient bone marrow-derived macrophages (BMDMs), we detected an increase in the induction of the LPS-induced pro-inflammatory signal nitric oxide (NO) but decreased IL-10 expression. The phosphorylation of ERK and p38 MAP-kinases was significantly decreased in stefin B-deficient macrophages, as was STAT-3 phosphorylation. These findings show that stefin B influences the expression of anti-inflammatory IL-10 in response to the TLR4 agonist LPS.
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana SI-1000, Slovenia; Jožef Stefan International Postgraduate School, Jamova 39, SI-1000 Ljubljana, Slovenia.
Katarina
K
Maher
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana SI-1000, Slovenia; Jožef Stefan International Postgraduate School, Jamova 39, SI-1000 Ljubljana, Slovenia.
Janja
J
Završnik
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana SI-1000, Slovenia; Jožef Stefan International Postgraduate School, Jamova 39, SI-1000 Ljubljana, Slovenia.
Barbara
B
Jerič-Kokelj
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana SI-1000, Slovenia.
Olga
O
Vasiljeva
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana SI-1000, Slovenia; Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins (CIPKeBiP), Jamova 39, SI-1000 Ljubljana, Slovenia; Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Cesta v Mestni log 88A, SI-1000 Ljubljana, Slovenia.
Boris
B
Turk
Department of Biochemistry, Molecular and Structural Biology, Jožef Stefan Institute, Ljubljana SI-1000, Slovenia. Electronic address: natasa.kopitar@ijs.si.
Nataša
N
Kopitar-Jerala
D000818:Animals; D002478:Cells, Cultured; D055313:Cystatin B / Q000172:deficiency* / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation / Q000276:immunology
C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016753:Interleukin-10; D009569:Nitric Oxide; D007371:Interferon-gamma; D055313:Cystatin B; D048049:Extracellular Signal-Regulated MAP Kinases
Cystatin; Interleukin-10; Lipopolysaccharide; MAP-kinase; Macrophage; Nitric oxide