Effects of paraquat and capsaicin on the expression of genes related to inflammatory, immune responses and cell death in immortalized human HaCat keratinocytes.
The present experiments were aimed to characterize in immortalized human HaCat keratinocytes the gene expression induced by paraquat and capsaicin, two agents known to induce cell death or to affect inflammatory and pain pathways, respectively. In particular, the following set of genes were analysed by qRealtime PCR: CXCL10,CXCL11, IL-10 (inflammatory and immune responses), TP73, BCL2, (apoptotic and anti-apoptotic genes), MMP9 (proteolysis), SOD-1, BAK-1 and CAT (peroxysomal and microsomal oxidation pathways). In this way, we were able to differentiate the two toxins since they had a different profile of gene expression. In fact, paraquata was found to activate set of genes involved in inflammatory (CXL10,CXL11 and IL-10), and cell death (BCL2, BAK-1, MMP9) pathways. Another specific site of action of paraquat was represented by an activation of the gene involved in SOD-1 transcription. On the contrary, capsaicin was found to produce only an up-regulation of BCL2, an anti-apoptotic gene and MMP9, whereas no significant changes were reported in genes involved in inflammatory and immune responses. Finally, in comparison to previous experiments carried out with TNF-alpha and IL-1beta, we have shown that paraquat produced a similar pattern of activation of set of genes involved both in inflammation and apoptosis.
IRCCS C. Mondino Institute of Neurology Foundation, Pavia.
N
N
Paolillo
S
S
Piccirilli
E
E
Giardina
V
V
Rispoli
C
C
Colica
S
S
Nisticò
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002211:Capsaicin / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics; D054371:Chemokine CXCL11 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010269:Paraquat / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics
C494772:BAK1 protein, human; C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D004268:DNA-Binding Proteins; C508609:IL10 protein, human; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C000606290:SOD1 protein, human; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D016753:Interleukin-10; D002374:Catalase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020780:Matrix Metalloproteinase 9; D010269:Paraquat; D002211:Capsaicin