Quantitative role of p42/44 and p38 in the production and regulation of cytokines TNF-alpha, IL-1beta and IL-12 by murine peritoneal macrophages in vitro by concanavalin A.
In the present study the quantitative role of p42/44 and p38 in the production of TNF-alpha, IL-1beta and IL-12 by murine peritoneal macrophages, in vitro, on treatment with Concanavalin A (ConA) has been investigated. Maximum expression/production of cytokines TNF-alpha, IL-1beta and IL-12 was observed after 16 h by RT-PCR and 24 h by ELISA, on in vitro treatment with ConA. To investigate the role of MAP kinases in the production of cytokines, pharmacological inhibitors of MAP kinases--PD98059, SB202190 and SP600125, were used. The expression of TNF-alpha, IL-1beta and IL-12 was down regulated in the presence of PD98059 and SB202190 in a dose dependent manner, suggesting the involvement of p42/44 and p38 in ConA induced production of TNF-alpha, IL-1beta and IL-12 by macrophages. It was observed that SP600125 did not have any effect on the expression of TNF-alpha, IL-1beta and IL-12. Using different combinations of MAPK inhibitors, it was found that 45% signal is conveyed via p42/44 and 25% via p38 in the production of these cytokines, by ConA treated macrophages while 30% signal passes through unidentified pathways.
Kesherwani
Varun
V
School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221005, India. varun.kesherwani@gmail.com
Sodhi
Ajit
A
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048290:Mitogen-Activated Protein Kinase 11 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D018664:Interleukin-12; D019950:Mitogen-Activated Protein Kinase 1; D048290:Mitogen-Activated Protein Kinase 11; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases