The role of surfactant protein D in chemotherapy-induced gastrointestinal toxicity in mice

Surfactant protein D (SP-D) is a host defense molecule produced by epithelial cells. SP-D is known for its role in pulmonary innate immunology, but is present in mucosa throughout the body. SP-D has been shown to be regulated in the gastrointestinal (GI-) mucosa of chemotherapy-treated piglets. Here, we investigated whether SP-D attenuates chemotherapy-induced GI inflammation and toxicity in mice.
SP-D knockout mice and wildtype littermates were treated with doxorubicin or saline and sacrificed three days post-administration. GI inflammation and toxicity was assessed by weight change and quantitative real-time PCR (qPCR) on GI samples.
Doxorubicin-treated mice showed significant weight loss, with SP-D knockout mice showing highest wasting. qPCR was performed for 11 genes related to GI inflammation and toxicity. Doxorubicin-treatment caused upregulation of TNF and downregulation of apoptosis-related genes. Effects were most pronounced in the jejunum, but showed similar effects in the colon. Doxorubicin-treated KO mice showed increased TNF expression in the colon and increased matrix metalloproteinase 2 in the jejunum.
Mucosal innate immune factors may be important in GI protection and homeostasis during chemotherapy. In the present study, we confirm that Doxorubicin-treatment causes vast GI inflammation and toxicity. SP-D appears to have limited effect on chemotherapy-induced GI toxicity and inflammation.