Three‐Tier Model for Inflammasome Expression and a New Concept of Inflammation Privilege

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We examined a new hypothesis that the tissue expressions of TLRs/NLRs/inflammasome/caspase‐1/IL‐1β pathway are differentially regulated. We made several findings: (1) Vascular tissues and heart express fewer types of TLRs and NLRs than immune tissues; and (2) Based on the expression data of inflammasomes (NALP1, NALP3 and IPAF), the tissues can be classified into three tiers: the first tier tissues including 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, require upregulation of at least two components to assemble functional inflammasomes. We examined the mRNA levels of inflammasome components in human aortic endothelial cells after stimulated with lipopolysaccharide (LPS). In the presence of LPS stimulation, the mRNA levels of the main inflammasome component including ASC, caspase‐1, NALP‐1 and NALP‐3 are up‐regulated, which supports our three‐tier model. Our original model of three‐tier expression of inflammasomes would further suggest a new concept of tissues’ inflammation privilege, which provides an important insight to the differences among tissues in initiating acute inflammation and upregulation of inflammasomes in inflammation‐privileged tissues in response to chronic metabolic stimuli.