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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Number of pages5
JournalExperimental Parasitology
DOIs
Publication statusAccepted/In press - 25 Mar 2015

Fingerprint

Acanthocheilonema
Oxazolone
Otitis
Ear
Inflammation
Allergic Contact Dermatitis
Phosphorylcholine
Mast Cells
Rodentia
Anti-Inflammatory Agents
Collagen
Cytokines
Messenger RNA
Skin
Pharmaceutical Preparations
Population

Keywords

  • ES-62
  • immunomodulation
  • oxazolone
  • parasitic worm
  • skin inflammation

Cite this

@article{11699363ab594f55be10da75200d0549,
title = "Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation",
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.",
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Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation. / Al-Riyami, Lamyaa; Rodgers, David T.; Rzepecka, Justyna; Pineda, Miguel A.; Suckling, Colin J.; Harnett, Margaret M.; Harnett, William.

In: Experimental Parasitology , 25.03.2015.

Research output: Contribution to journalArticle

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AU - Al-Riyami, Lamyaa

AU - Rodgers, David T.

AU - Rzepecka, Justyna

AU - Pineda, Miguel A.

AU - Suckling, Colin J.

AU - Harnett, Margaret M.

AU - Harnett, William

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AB - 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.

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