Mechanism of rLcrV and rYopB mediated Immunosuppression in murine peritoneal macrophages.
Yersinia pestis causative organism of bubonic and pneumonic plague uses type III secretion system for the translocation of effector molecules in to the target host cells. Type III secretion system of Yersinia pestis, secretes Low calcium response V (LcrV) or V antigen and many other Yersinia outer proteins (Yops). LcrV and YopB were initially known as translocator proteins, but recently have been shown to act as effector and regulatory proteins. Macrophages participate actively in immune response by secreting various effector molecules or by phagocytosis in clearing most of the pathogens. We investigated the effect of rLcrV and rYopB (10 microg/ml) on peritoneal macrophages in vitro. It is observed that rLcrV and rYopB inhibited LPS induced TNF-alpha and NO production in murine peritoneal macrophages. rLcrV and rYopB also inhibited expression of phospho-p38, -p42/44, -JNK MAPKs and transcription factors NFkappaB, c-fos and c-jun in LPS treated macrophages. The inhibition in the expression of these signaling molecules has been correlated to the inhibition of TNF-alpha and NO production in macrophages.
Sodhi
Ajit
A
School of Biotechnology, BHU, Varanasi, UP 221005, India. ajit.sodhi@lycos.com
Sharma
Rajesh K
RK
Batra
Harsh V
HV
Tuteja
Urmil
U
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D019286:Endopeptidase K / Q000378:metabolism; D051550:I-kappa B Kinase; D007108:Immune Tolerance / Q000276:immunology / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D052899:Pore Forming Cytotoxic Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014409:Tumor Necrosis Factor-alpha; C078909:YopB protein, Yersinia; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; D020928:Mitogen-Activated Protein Kinases; D019286:Endopeptidase K