Down-regulated expression of TWEAK mRNA in acute and chronic inflammatory pathologies

TWEAK is a newly identified member of the Tumor Necrosis Factor (TNF) famil y of proteins which are involved in many immunoinflammatory mechanisms. The putative role of TWEAK in inflammation was analyzed in mice treated with l ipopolysaccharide (LPS), a strong inducer of the immuno-inflammatory respon ses. TWEAK mRNA rapidly disappeared in all the tissues tested. Analysis of LPS-treated thioglycolate-elicited peritoneal macrophages revealed that the rapid loss of TWEAK mRNA was due to its active destabilization. In chronic pathologies like autoimmune hemolytic anemia in the NZB mouse strain or sy stemic lupus erythematosus (SLE) in the BXSB mouse strain, TWEAK mRNA was s hown to be reduced concomitantly to the development of chronic autoimmune d iseases. These results demonstrated that TWEAK mRNA contrary to TNF mRNA, i s stable, ubiquitously distributed in tissues, and is down-regulated after LPS treatment or in chronic inflammation, suggesting that TWEAK could be an important factor, along with TNF, in acute and chronic inflammations. (C) 2000 Academic Press.