SJSZ glycoprotein (38 kDa) prevents thymus atrophy and enhances expression of IL-2 and IL-12 in diethylnitrosamine-induced hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is a typical inflammation-associated cancer, but has also been shown to provoke antitumor immune responses. Polarized T helper type 2 (Th2) responses down-regulate antitumor immunity to link with HCC. The objective of this study was to investigate the protective effect of the Styrax japonica Siebold et al. Zuccarini (SJSZ) glycoprotein on thymus atrophy and differential response of Th1/Th2 cells induced by diethlynitrosamine (DEN). To evaluate the modulatory effect of the SJSZ glycoprotein on thymic atrophy and imbalanced Th1/Th2 cells, we examined the weight of the thymus, [3H]-thymidine incorporation and expression of proliferating cell nuclear antigen (PCNA), and activities of protein kinase C (PKC)/intracellular Ca2+, extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, T-box transcription factor (T-bet), GATA-binding protein-3 (GATA-3), cytokines [interleukin (IL)-4, -10, -2, -12 and interferon (IFN)-γ] using radioactivity, immunoblot analysis, and qRT-PCR. The SJSZ glycoprotein (10 mg/kg, BW) was shown to increase the weight of the thymus, [3H]-thymidine incorporation and PCNA in thymocytes induced by DEN. Also, it increased expression levels of T-bet and Th1 cytokines (IFN-γ, IL-2 and IL-12). However, the activity of PKC/intracellular Ca2+, phosphorylation of ERK and p38 MAPK, expression levels of GATA-3 and Th2 cytokines (IL-4 and IL-10) were decreased. Taken together, these results suggest that the SJSZ glycoprotein can prevent thymic atrophy and Th2 cytokines induced by DEN.

► Polarized T helper type 2 response is linked with hepatocellular carcinoma.
► SJSZ glycoprotein prevents thymic atrophy in Balb/c mice induced by DEN.
► It enhances T-bet and Th1 cytokines (IFN-γ, IL-2 and IL-12).
► The activities of GATA-3, p-STAT6 and Th2 cytokines (IL-4 and IL-10) were decreased.
► SJSZ glycoprotein can prevent thymic atrophy and Th2 cytokines induced by DEN.