Relationship of TSG-14 protein to the pentraxin family of major acute phase proteins

TNF-stimulated gene-14 (TSG-14) encodes a secreted glycoprotein with significant sequence homology to C-reactive protein (CRP) and serum amyloid P component (SAP), members of the pentraxin family of acute phase proteins. TSG-14 mRNA was elevated in human FS-4 fibroblasts by treatment with TNF, IL- 1, or bacterial LPS, and weakly by dexamethasone. Abs to recombinant TSG-14 immunoprecipitated a 42-kDa protein from the culture supernatants of TNF- or IL-1-stimulated FS-4 cells. TSG-14 protein was also inducible in the Hep3B human hepatoma cell line by TNF, IL-1, IL-6, or dexamethasone. CRP protein, identified by immunoprecipitation of a 25-kDa band with Abs to CRP, was induced in Hep3B cells by IL-1, IL-6, or dexamethasone. Immunoprecipitations with polyclonal Abs to TSG-14 and CRP suggested that the two proteins are immunologically cross-reactive. Appearance of TSG-14 protein was demonstrated in the serum of mice after injection with LPS. No TSG-14 mRNA was detected in the liver of LPS-injected mice, suggesting that hepatocytes are not the major site of TSG-14 synthesis. Thus, in the intact organism the main cellular sources of TSG-14 and classical acute phase proteins appear to be different.