Inflammasomes are differentially expressed in cardiovascular and other tissues.
To determine the expression of components in Toll-like receptors (TLRs)/Nod-like receptors (NLRs)/inflammasome/caspase-1/interleukin (IL-1)-beta pathway, we examined the expression profiles of those genes by analyzing the data from expression sequence tag cDNA cloning and sequencing. We made several important findings: firstly, among 11 tissues examined, vascular tissues and heart express fewer types of TLRs and NLRs than immune and defense tissues including blood, lymph nodes, thymus and trachea; secondly, brain, lymph nodes and thymus do not express proinflammatory cytokines IL-1beta and IL-18 constitutively, suggesting that these two cytokines need to be upregulated in the tissues; and thirdly, based on the expression data of three characterized inflammasomes (NALP1, NALP3 and IPAF inflammasome), the examined tissues can be classified into three tiers: the first tier tissues including brain, placenta, blood and thymus express inflammasome(s) in constitutive status; the second tier tissues have inflammasome(s) in nearly-ready expression status (with the requirement of upregulation of one component); the third tier tissues, like heart and bone marrow, require upregulation of at least two components in order to assemble functional inflammasomes. Our original model of three-tier expression of inflammasomes would suggest a new concept of tissue inflammation privilege, and provides an insight to the differences among tissues in initiating acute inflammation in response to stimuli.
Yin
Y
Y
Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, USA.
Yan
Y
Y
Jiang
X
X
Mai
J
J
Chen
N C
NC
Wang
H
H
Yang
X-F
XF
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D002319:Cardiovascular System / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; D053472:Nod Signaling Adaptor Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C435692:NLRC4 protein, human; C427903:NLRP1 protein, human; C453881:NLRP3 protein, human; D053472:Nod Signaling Adaptor Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha