论文部分内容阅读
BACKGROUND:?Ron? receptor? tyrosine? kinase? signaling? in?macrophages,?including?Kupffer?cells?and?alveolar?macrophages,?suppresses? endotoxin-induced? proinlfammatory? cytokine/chemokine?production.?Further,?we?have?also?identiifed?genes?from?Ron?replete?and?Ron?deplete?livers?that?were?differentially?expressed? during? the? progression? of? liver? inlfammation?associated?with?acute?liver?failure?in?mice?by?microarray?analyses.?While? important? genes? and? signaling? pathways? have? been?identiifed?downstream?of?Ron?signaling?during?progression?of?inlfammation?by?this?approach,?the?precise?role?that?Ron?receptor?plays?in?regulating?the?transcriptional?landscape?in?macrophages,?and?particular?in?isolated?Kupffer?cells,?has?still?not?been?investigated. METHODS:?Kupffer?cells?were?isolated?from?wild-type?(TK+/+)?and?Ron?tyrosine?kinase?deifcient?(TK-/-)?mice.?Ex vivo,?the?cells?were?treated?with?lipopolysaccharide?(LPS)?in?the?presence?or?absence?of?the?Ron?ligand,?hepatocyte?growth?factor-like?protein?(HGFL).?Microarray?and?qRT-PCR?analyses?were?utilized?to?identify?alterations?in?gene?expression?between?genotypes. RESULTS:?Microarray? analyses? identiifed? genes? expressed?differentially?in?TK+/+?and?TK-/-?Kupffer?cells?basally?as?well?as?after?HGFL?and?LPS?treatment.?Interestingly,?our?studies?identiifed?Mefv,?a?gene?that?codes?for?the?anti-inlfammatory?protein?pyrin,?as?an?HGFL-stimulated?Ron-dependent?gene.?Moreover,?lipocalin?2,?a?proinlfammatory?gene,?which?is?induced?by? LPS,? was? signiifcantly? suppressed? by? HGFL? treatment.?Microarray? results? were? validated? by? qRT-PCR? studies? on?Kupffer?cells?treated?with?LPS?and?HGFL. CONCLUSION:?The?studies?herein?suggest?a?novel?mechanism?whereby? HGFL-induced? Ron? receptor? activation? promotes?the?expression?of?anti-inlfammatory?genes?while?inhibiting?genes?involved?in?inlfammation?with?a?net?effect?of?diminished?inlfammation?in?macrophages.