title: Expression analysis of inflammasomes in experimental models of inflammatory and fibrotic liver disease.
abstract: During inflammation, the inflammasomes representing a group of multi-protein complexes trigger the biological maturation of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 by proteolytic activation of caspase-1 from its inactive proforms. The individual genes encoding components of the inflammasome machinery are regulated at transcriptional and post-transcriptional levels. Once activated, they drive a wide variety of cellular responses that are necessary to mediate host defense against microbial pathogens and to guarantee tissue homeostasis. In the present work, we have studied the expression of the different inflammasomes in various primary hepatic cell subpopulations, in models of acute inflammation and during experimental liver fibrogenesis. We demonstrate that NLRP-1, NLRP-3 and AIM2 are prominently expressed in Kupffer cells and liver sinusoidal endothelial cells, moderately expressed in periportal myofibroblasts and hepatic stellate cells, and virtually absent in primary cultured hepatocytes. We found that the challenge with the lipopolysaccharides results in a time- and concentration-dependent expression of the NOD-like receptor family members NLRP-1, NLRP-3 and NLRC4/NALP4 in cultured hepatic stellate cells and a strong transcriptional activation of NLRP-3 in hepatocytes. Moreover, we detect a diverse regulatory network of the different inflammasomes in the chosen experimental models of acute and chronic liver insult suggesting that the various inflammasomes might contribute simultaneously to the outcome of inflammatory and fibrotic liver insult, irrespectively of the underlying inflammatory stimulus.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstr. 30, Aachen D-52074, Germany.
authors.forename: Sorina Georgiana
authors.initials: SG
authors.lastname: Boaru
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstr. 30, Aachen D-52074, Germany.
authors.forename: Erawan
authors.initials: E
authors.lastname: Borkham-Kamphorst
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstr. 30, Aachen D-52074, Germany.
authors.forename: Lidia
authors.initials: L
authors.lastname: Tihaa
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstr. 30, Aachen D-52074, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Haas
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital Aachen, Pauwelsstr. 30, Aachen D-52074, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen