Figure 1

Proposed basis for the antagonistic actions of PH-20 and TGF-β1 on L929 cell susceptibility to TNF cytotoxicity. Testicular hyaluronidase PH-20 enhances TNF cytotoxicity in L929 fibroblasts (see green), whereas TGF-β1 induces TNF-resistance in these cells (see red). Both upregulation of proapoptotic p53 and WOX1 and downregulation of antiapoptotic matrix inter-α-inhibitor are involved in the PH-20-increased TNF susceptibility in L929 cells [8–10]. Also, PH-20 rapidly activates ERK (or p42/44 MAPK) and c-Jun N-terminal kinases (JNK1 and JNK2) [16]. In contrast, TGF-β1 protects L929 cells from TNF cytotoxicity by upregulating antiapoptotic TIAF1, TIF2 and a novel matrix protein [11–14]. TGF-β1 counteracts PH-20-induced TNF-susceptibility in L929 cells [8]. TGF-β1 suppresses PH-20-mediated ERK activation [16], whereas ERK activation is not related with PH-20-increased TNF susceptibility in L929 cells [15]. Whether the proapoptotic p53 and WOX1 block the antiapoptotic function of TIAF1 and TIF2 is not known.