Leishmanial lipid suppresses the bacterial endotoxin-induced inflammatory response with attenuation of tissue injury in sepsis.
The use of live, attenuated, or genetically modified microbes or their cellular component(s) or metabolites has begun to emerge as a potential new approach in medicinal research to deliver biologically active entities. Thus, advancing our knowledge of such microbe-mediated therapy may suggest new avenues for therapeutic intervention in many diseases. We had earlier reported that the total lipid of attenuated Leishmania donovani suppressed the inflammatory responses in rheumatoid arthritis patients. Our present study reveals that the pLLD, isolated from pathogenic L. donovani, decreases the inflammatory level of bacterial endotoxin in stimulated mouse macrophages, as also in the in vivo murine system. It exerts the activity by reducing the level of different mediators, such as cytokine-chemokine(s). It also suppresses the expression of the ubiquitous transcription factor NF-κBp65 in stimulated macrophage cells, improves the endotoxin-associated liver damage, reduces the vascular permeability factors, such as VEGF, and suppresses the expression of cell adhesion molecules, including ICAM-1, VCAM-1, PECAM-1, P-selectin, and E-selectin, in liver of septic mice. These findings indicate that pLLD may prove to be a potential anti-inflammatory agent and protect from endotoxin-induced sepsis in hepatic impairment.
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, West Bengal, India; and.
Nabanita
N
Chatterjee
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, West Bengal, India; and.
Subhadip
S
Das
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, West Bengal, India; and.
Dipayan
D
Bose
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, West Bengal, India; and.
Somenath
S
Banerjee
Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Tarun
T
Jha
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology, West Bengal, India; and krishnaiicb@yahoo.com.
Krishna Das
KD
Saha
D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007893:Leishmania donovani / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000276:immunology / Q000293:injuries* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D051996:Transcription Factor RelA / Q000276:immunology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D008055:Lipids; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C440499:lipopolysaccharide, Escherichia coli O111 B4
Leishmania; inflammation; lipopolysaccharide; macrophage; septic damage