Serum amyloid P ameliorates radiation-induced oral mucositis and fibrosis

Abstract

PurposeTo evaluate the effect of the anti-fibrotic protein serum amyloid P (SAP) on radiation-induced oral mucositis (OM) and fibrosis in a hamster cheek-pouch model.Experimental DesignHamsters received a single dose of radiation (40 Gy) to the left everted cheek pouch to induce significant OM. The protective therapeutic potential of SAP was evaluated using varying dosing regimens. The extent of OM was measured using a validated six-point scoring scheme ranging from 0 (normal tissue, no mucositis) to 5 (complete ulceration). Fibrotic remodeling was also visualized histologically and quantified at later time points using collagen gene expression.ResultsSAP treatment attenuated the profile of radiation-induced oral mucositis by delaying the time of onset, reducing the peak value, and enhancing the resolution of injury. The peak mucositis score was reduced by approximately 0.5 grade in SAP-treated animals. The number of animal days with a score of ≥ 3 was reduced by 48% in the SAP-treated group, compared with the saline control group (P < 0.01). SAP also inhibited the extent of tissue remodeling and decreased radiation-induced increases in myofibroblast number. Attenuated collagen deposition and gene expression was also observed in the cheek pouches of hamsters treated with SAP at both 16 and 28 days post-radiation.ConclusionsSAP treatment significantly attenuated radiation-induced injury. In particular, SAP attenuated the severity of OM and inhibited pathogenic remodeling. This suggests that SAP may be a useful therapy for the palliation of side effects observed during treatment for head and neck cancer.

Brain Serum Amyloid P Levels are Reduced in Individuals that Lack Dementia While Having Alzheimer’s Disease Neuropathology

“…SAP is a pattern recognition protein that binds components of pathogens as well as apoptotic and autoimmune material [12,13]. SAP is involved in wound repair and the innate immune response [14–16], and is a potent regulator of monocyte responses controlling fibrosis [17–21]; however, SAP also potentially contributes to the pathogenesis of Alzheimer’s disease through the binding of amyloid plaques and neurofibrillary tangles (NFTs) [22–24]. SAP has been found to enter neurons, and at elevated levels can induce apoptosis in vitro and in vivo [25,26].…”

Novel association between serum pentraxin‐2 levels and advanced fibrosis in well‐characterised patients with non‐alcoholic fatty liver disease

“…The pre-clinical data on administration of exogenous PTX-2 has shown significant benefit in models of several chronic fibrotic diseases, including bleomycin-or TGF-induced lung fibrosis, 12,40,41 ischaemia reperfusion injury, 7 corneal injury, 42 and radiation-induced oral mucositis and fibrosis. 43 Importantly, pre-clinical testing in models of chronic liver disease including CCl4-and bile duct ligation-induced liver fibrosis were similarly encouraging. 14 When these liver-injured mice were treated with recombinant PTX-2, fibrosis development was significantly inhibited, as was the activation of fibrogenic myofibroblasts, inflammatory cytokines (IL-1b, IL-6 and TNF-a), and pro-fibrogenic genes (e.g.…”

“…As PTX‐2 is known to play an important role in the inhibition of hepatic stellate cell activation as well as in the regulation of fibrogenesis and wound healing, repletion with recombinant protein is a promising therapeutic target. The pre‐clinical data on administration of exogenous PTX‐2 has shown significant benefit in models of several chronic fibrotic diseases, including bleomycin‐ or TGF‐induced lung fibrosis, ischaemia reperfusion injury, corneal injury, and radiation‐induced oral mucositis and fibrosis . Importantly, pre‐clinical testing in models of chronic liver disease including CCl4‐ and bile duct ligation‐induced liver fibrosis were similarly encouraging .…”

Histopathologic grading of oral mucositis

“…This claim was supported by studies that demonstrated that suppression of reactive oxygen species with superoxide dismutase (Murphy et al , ) or the inhibition of cytokines favorably alters the disease course (Sonis, ). Mitigation of oral mucositis with serum amyloid P, a protein instrumental in curtailing disproportionate fibrotic response in damaged tissues, further strengthened the significance of submucosal tissue response in disease development (Murray et al , ).…”