Soluble gp130 promotes intestinal epithelial hyperplasia during reovirus infection

Abstract

Soluble gp130 (sgp130) has been shown to suppress the inflammatory response of autoimmune pathologies; however, its effects on virus infection are not known. Here, we report that intraperitoneal treatment of mice with sgp130-Fc fusion protein at the time of oral reovirus serotype 3 infection resulted in altered morphopathological changes that were evident by less shortening of intestinal villi length and crypt depth after infection. That the effect mediated by sgp130 treatment was due to an increase in intestinal crypt cell proliferation was demonstrated by an increase in the number of crypt mitotic figures. This was further confirmed by increased immunoreactivity to the Cdc47 proliferation-associated antigen in crypts of sgp130-treated virus-infected mice compared to infected non-treated mice. These findings suggest that sgp130 may have a beneficial effect during intestinal virus infection by disrupting interleukin-6 trans-signalling, thereby reducing the local inflammatory response.

Figure 1

T3D reovirus gene expression at days 2, 4, and 6 post-infection in small intestinal tissues from non-treated and sgp130-treated infected mice. Data are mean values ± SEM; statistically-significant difference (*P< 0.05). No viral RNA was detected in non-infected mice (data not shown).

Figure 2

(a) Villi length and (b) crypt depths at days 2, 4, and 6 post-infection in small intestinal tissues from non-treated and sgp130-treated infected mice. Panels C-E are representative tissue sections from reovirus-infected mice without (d) and with (e) sgp130 treatment at the day 6 post-infection time point, and (c) a tissue section of a normal non-infected mouse. Bars are 100 μm. Data are mean values ± SEM; treatment with sgp130 resulted in statistically-significant less (*P< 0.05; **P< 0.01) villus and crypt shortening at all time points. Statistically shorter (**P< 0.05) crypt length compared to non-infected mice.

Figure 3

(a) Treatment of reovirus-infected mice with sgp130 resulted in statistically-significant (*P< 0.05; **P< 0.01) more cells undergoing mitosis at days 2, 4, and 6 post-infection compared to non-treated infected mice. Statistically fewer (*,**P< 0.01) crypt mitotic figures compared to non-infected mice. (b) Example of Cdc47 staining. (c) Crypts of reovirus-infected mice treated with sgp130 had statistically-significant (P < 0.01) more Cdc47⁺ cells compared to infected non-treated mice. Data are mean values ± SEM.