Exposure to lanthanum compound diminishes LPS-induced inflammation-associated gene expression: involvements of PKC and NF-kappaB signaling pathways.
Lanthanum chloride, a rare earth compound, possesses antibacterial and cellular immunity regulating properties. However, the underlying molecular mechanisms remain largely unknown. In this study, we examined the effects of lanthanum chloride on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), the expression of inducible NO synthase (iNOS) and TNF-alpha in RAW 264.7 cells, a mouse macrophage cell line. We found that the LPS-elicited excessive production of NO and TNF-alpha in RAW 264.7 cells was inhibited significantly in the presence of lanthanum chloride, and the attenuation of iNOS and TNF-alpha occurred at mRNA level. Furthermore, the possible signaling components affected by lanthanum chloride in the pathway that lead to LPS-induced iNOS and TNF-alpha expression were explored. The results indicated the involvements of PKC/Ca(2+) and NF-kappaB in the attenuation of NO and pro-inflammatory cytokine production by lanthanum chloride. Our observations suggest a possible therapeutic application of this agent for treating inflammatory diseases.
Guo
Fei
F
Burns Institute, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People's Republic of China.
Lou
Yuanlei
Y
Feng
Nianhua
N
Li
Guohui
G
Xie
An
A
Huang
Xueming
X
Wang
Yang
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced* / Q000276:immunology; D007811:Lanthanum / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C028521:lanthanum chloride; D009569:Nitric Oxide; D007811:Lanthanum; D052247:Nitric Oxide Synthase Type II; D011493:Protein Kinase C; D002118:Calcium