Browsing by Author "Harsh Vardhan Batra"

Now showing 1 - 5 of 5

Effect of rLcrV and rYopB from Yersinia pestis on murine peritoneal macrophages in vitro
(Elsevier, 2004) Rajesh Kumar Sharma; Ajit Sodhi; Harsh Vardhan Batra; Urmil Tuteja
The interaction between macrophages and bacterial pathogens is crucial in the pathogenesis of infectious diseases. The 70 kb plasmid encodes low calcium response V (LcrV) or V antigen and a group of highly conserved yersinia outer proteins (Yops) are essential for full virulence. In present study, we investigated the effect of rLcrV and rYopB on macrophage functions in vitro. It is observed that rLcrV and rYopB inhibited the LPS induced expression of TNF-α, IFN-γ, KC, IP-10, and IL-12 in macrophages. rLcrV and rYopB caused increased expression of IL-10 and TLR2, whereas inhibited TLR4 expression in LPS treated macrophages. IL-10 and TLR2 antibodies reversed the rLcrV and rYopB induced inhibition of TNF-α production by LPS treated macrophages, whereas IL-4 and TLR4 antibodies had no effect. Our data suggests a possible role of IL-10 and TLR2 in rLcrV and rYopB mediated inhibition of macrophage function. © 2004 Elsevier B.V. All rights reserved.
Erratum: Effect of rLcrV and rYopB from Yersinia pestis on murine peritoneal macrophages in vitro (Immunology Letters (2004) 93:2-3 (179-187) DOI: 10.1016/j.imlet.2004.03.010)
(2006) Rajesh Kumar Sharma; Ajit Sodhi; Harsh Vardhan Batra; Urmil Tuteja
[No abstract available]
Involvement of c-Jun N-terminal kinase in rF1 mediated activation of murine peritoneal macrophages in vitro
(2005) Rajesh Kumar Sharma; Ajit Sodhi; Harsh Vardhan Batra
Fraction 1 (F1) protein forms a capsule on the surface of Yersinia pestis. Recently, we reported rF1-induced activation of macrophages. In current investigation, we studied the role of JNK MAPK signal transduction pathway in rF1-induced activation of macrophages in vitro. SP600125, a specific inhibitor of JNK, inhibited JNK MAPK phosphorylation, indicating the specificity of the above response. Though, the rF1-induced phosphorylation of JNK MAPK was also inhibited by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor genestein and PI3-K inhibitor wotmannin. Activation of the transcription factor NF-kB (phosphorylation of IkB) and c-Jun was observed in response to rF1 treatment. The rF1-induced JNK MAPK activity was correlated to the functional activation of macrophages by demonstrating the inhibition of NO, TNF-α production and microtubule polymerization caused by SP600125. Taken together, the data suggests the involvement of JNK MAPK/NF-kB pathway in rF1-induced activation of macrophages. © 2005 Springer Science+Business Media, Inc.
Involvement of TLR6/1 in rLcrV-mediated immunomodulation of murine peritoneal macrophages in vitro
(Elsevier Ltd, 2005) Rajesh Kumar Sharma; Ajit Sodhi; Harsh Vardhan Batra
LcrV of Yersinia pestis is an enigmatic antigenic protein having multiple functions such as effector, translocator and regulator in Type III secretion system. In present study, it is reported that rLcrV causes subversion of macrophage-mediated immune functions. rLcrV treatment down regulated the transcription of IL-12, IRAK-1, MHC-II, phosho-STAT1 and adhesion molecule CD18 in LPS stimulated macrophages. rLcrV induced up regulation of phospho-STAT3 expression, while had no effect on expression of phospho-STAT6. Neutralization and immunoprecipitation experiments suggest the probable involvement of TLR2 and TLR6 heterodimer in rLcrV-mediated immunomodulation of macrophages. Adaptor molecule MyD88, CD11b, and MHC-I expression did not modulate upon treatment with rLcrV. © 2004 Elsevier Ltd. All rights reserved.
Phosphorylation of p42/44 MAP kinase is required for rF1-induced activation of murine peritoneal macrophages
(2005) Rajesh Kumar Sharma; Ajit Sodhi; Harsh Vardhan Batra; Urmil Tuteja
The Fraction 1 (F1) antigen of Yersinia pestis is known to induce thymocyte proliferation. It serves as a major protective antigen against challenge of Y. pestis. Recently, we reported rF1-induced activation of macrophages. Current investigation elucidates the role of p42/44 mitogen-activated protein kinases (MAPK)-mediated signal transduction in murine peritoneal macrophages on stimulation with rF1 (10 μg/ml) in vitro. The p42/44 MAPK activation was determined by studying the expression of the phosphorylated p42/44 MAPK in rF1-treated macrophages. PD98059, a specific inhibitor of MAPK kinase (MEK) inhibited the p42/44 MAPK phosphorylation, indicating the specificity of the above response. Furthermore, the rF1-induced phosphorylation of p42/44 MAPK is found to blocked by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor genistein and phosphoinositol-3-kinase (PI3-K) inhibitor wortmannin. Additionally, phosphorylation of JNK and activation of the transcription factor, c-jun and c-fos was also observed in response to rF1 treatment. The rF1-induced activation of p42/44 MAPK was correlated to the functional activation of macrophages by demonstrating the inhibition of actin rearrangement, IL-1, TNF-α and NO production caused by PD98059 in the rF1-treated macrophages. © 2005 Elsevier Ltd. All rights reserved.