Involvement of tyrosine kinases and MAP kinases in the production of TNF-alpha and IL-1beta by macrophages in vitro on treatment with phytohemagglutinin.
Treatment of murine peritoneal macrophages with various doses of phytohemagglutinin (PHA) for different time intervals enhanced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Maximum transcription for TNF-alpha and IL-1beta was observed at 16 h, whereas maximum production was observed at 24 h of PHA treatment. The most optimum dose was 1 mug/mL PHA. Pharmacologic inhibitors of tyrosine kinase, p42/44, p38, and JNK downregulate the PHA-induced expression of TNF-alpha and IL-1beta. Maximum protein tyrosine kinase (PTK) activity in macrophages was seen at 5 min of PHA-treatment. PHA-treated macrophages showed maximum expression of phospho-p42/44 and phospho-JNK at 15 min. It was also observed that p38 is activated after 12 h of PHA treatment. Pharmacologic inhibitor of tyrosine kinase, genistein down-regulated the PHA-induced activation of p42/44 and JNK.
Kesherwani
Varun
V
School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi-221005, India.
Sodhi
Ajit
A
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D027805:Phaseolus / Q000737:chemistry; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D053583:Interleukin-1beta; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases