Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation

Lamyaa Al-Riyami,David T Rodgers,Justyna Rzepecka,Miguel A Pineda,Colin J Suckling,Margaret M Harnett,William Harnett

doi:10.1016/j.exppara.2015.03.025

Lamyaa Al-Riyami, David T Rodgers + Show 5 more

Open Access

https://doi.org/10.1016/j.exppara.2015.03.025

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Abstract

ES-62 is the major secreted protein of the rodent filarial nematode Acanthocheilonema viteae. The molecule contains covalently attached phosphorylcholine (PC) residues, which confer anti-inflammatory properties on ES-62, underpinning the idea that drugs based on this active moiety may have therapeutic potential in human diseases associated with aberrant inflammation. Here we demonstrate that two synthetic small molecule analogues (SMAs) of ES-62 termed SMA 11a and SMA 12b are protective in the oxazolone-induced acute allergic contact dermatitis mouse model of skin inflammation, as measured by a significant reduction in ear inflammation following their administration before oxazolone sensitisation and before oxazolone challenge. Furthermore, it was found that when tested, 12b was effective at reducing ear swelling even when first administered before challenge. Histological analysis of the ears showed elevated cellular infiltration and collagen deposition in oxazolone-treated mice both of which were reduced by treatment with the two SMAs. Likewise, the oxazolone-induced increase in IFNγ mRNA in the ears was reduced but no effect on other cytokines investigated was observed. Finally, no influence on the mast cell populations in the ear was observed.

Highlights

A major cause of occupational skin disease is allergic contact dermatitis, which accounts for around 20% of all work-related health complaints
Its anti-inflammatory properties led to it being tested in both the collagen-induced arthritis (CIA) model of rheumatoid arthritis (Harnett et al, 2008; McInnes et al, 2003; Pineda et al, 2012) and the ovalbumin-induced airway hypersensitivity (OAH) model of asthma (Melendez et al, 2007; Rzepecka et al, 2013) where in both cases it was found to protect against disease development
The ears were fixed in 10% formalin for at least significantly reduced (31.3 ± 1.38% of the increase in ear thickness observed in the oxazolone group relative to the non-sensitised control)

Summary

Introduction

A major cause of occupational skin disease is allergic contact dermatitis, which accounts for around 20% of all work-related health complaints. The mouse oxazolone contact hypersensitivity model is an experimental model system, which is employed to study human allergic contact dermatitis and has provided the framework for understanding of the human disease (Jin et al, 2009; Kaplan et al, 2012; Lundberg et al, 2012). Its anti-inflammatory properties led to it being tested in both the collagen-induced arthritis (CIA) model of rheumatoid arthritis (Harnett et al, 2008; McInnes et al, 2003; Pineda et al, 2012) and the ovalbumin-induced airway hypersensitivity (OAH) model of asthma (Melendez et al, 2007; Rzepecka et al, 2013) where in both cases it was found to protect against disease development. We employed the oxazolone-induced acute allergic contact dermatitis mouse model to test the ability of SMAs 11a and 12b to modulate skin inflammation. We show that both 11a and 12b are effective at reducing ear swelling and this is associated with a clear reduction in cellular infiltration and collagen deposition as shown by histological analysis

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