TLR4-independent and PKR-dependent interleukin 1 receptor antagonist expression upon LPS stimulation.
Dendritic cells (DCs) induce innate immune responses by recognizing bacterial LPS through TLR4 receptor complexes. In this study, we compared gene expression profiles of TLR4 knockout (TLR4(neg)) DCs and wild type (TLR4(pos)) DCs after stimulating with LPS. We found that the expression of various inflammatory genes by LPS were TLR4-independent. Among them, interleukin 1 receptor antagonist (IL-1rn) was of particular interest since IL-1rn is a potent natural inhibitor of proinflammatory IL-1. Using RT-PCR, real-time PCR, immunoblotting and ELISA, we demonstrated that IL-1rn was induced by DCs stimulated with LPS in the absence of TLR4. 2-Aminopurine, a pharmacological PKR inhibitor, completely abrogated LPS-induced expression of IL-1rn in TLR4(neg) DCs, suggesting that LPS-induced TLR4-independent expression of IL-1rn might be mediated by PKR pathways. Considering that IL-1rn is a physiological inhibitor of IL-1, TLR4-independent and PKR-dependent pathways might be crucial in counter-balancing proinflammatory effector functions of DCs resulted from TLR4-dependent activation by LPS.
Na
Hye Young
HY
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Mazumdar
Kaushiki
K
Moon
Hye-Jung
HJ
Chang
Sooghee
S
Seong
Seung-Yong
SY
D015075:2-Aminopurine / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020869:Gene Expression Profiling; D053590:Interleukin 1 Receptor Antagonist Protein / Q000819:agonists / Q000096:biosynthesis* / Q000276:immunology; D037102:Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D037102:Lectins; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D015075:2-Aminopurine; D019892:eIF-2 Kinase