Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice

Matthew L. Renninger, Rosemarie E. Seymour, Laurence O. Whiteley, John P. Sundberg, Harm HogenEsch

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Sharpin-deficient (Sharpincpdm) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil-depletion in chronic inflammation, Sharpincpdm mice were treated with anti-IL5 antibodies. Mice treated with anti-IL5 had a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils after 10 days compared with sham-treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride-binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation. Skin homogenates from mice treated with anti-IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, kit ligand (Kitl) and Tgfa; and increased mRNA expression of Tgfb1, Mmp12 and tenascin C (Tnc). In order to further decrease the accumulation of eosinophils, Sharpincpdm mice were crossed with IL5 null mice. Il5-/-, Sharpincpdm/Sharpincpdm mice had a 98% reduction of circulating eosinophils and a 95% decrease in cutaneous eosinophils compared with IL5-sufficient Sharpincpdm mice. The severity of the lesions was similar between IL5-sufficient and IL5-deficient mice. Double mutant mice had a significant decrease in Abp1, and a significant increase in Tgfb1, Mmp12 and Tnc mRNA compared with controls. These data indicate that eosinophils are not essential for the development of dermatitis in Sharpincpdm mice and suggest that eosinophils have both pro-inflammatory and anti-inflammatory roles in the skin of these mice.

Original languageEnglish (US)
Pages (from-to)252-258
Number of pages7
JournalExperimental Dermatology
Volume19
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Dermatitis
Interleukin-5
Eosinophils
Amine Oxidase (Copper-Containing)
Tenascin
Skin
Messenger RNA
N-Acetylgalactosamine-4-Sulfatase
Stem Cell Factor
sharpin
Amiloride
Interleukin-10
Inflammation
Carrier Proteins
Anti-Inflammatory Agents
Alopecia
Erythema

Keywords

  • Antibodies
  • Atopic dermatitis
  • Eosinophils
  • Interleukin-5
  • Mice

ASJC Scopus subject areas

  • Dermatology
  • Molecular Biology
  • Biochemistry

Cite this

Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice. / Renninger, Matthew L.; Seymour, Rosemarie E.; Whiteley, Laurence O.; Sundberg, John P.; HogenEsch, Harm.

In: Experimental Dermatology, Vol. 19, No. 3, 03.2010, p. 252-258.

Research output: Contribution to journalArticle

Renninger, Matthew L. ; Seymour, Rosemarie E. ; Whiteley, Laurence O. ; Sundberg, John P. ; HogenEsch, Harm. / Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice. In: Experimental Dermatology. 2010 ; Vol. 19, No. 3. pp. 252-258.
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abstract = "Sharpin-deficient (Sharpincpdm) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil-depletion in chronic inflammation, Sharpincpdm mice were treated with anti-IL5 antibodies. Mice treated with anti-IL5 had a 90{\%} reduction of circulating eosinophils and a 50{\%} decrease in cutaneous eosinophils after 10 days compared with sham-treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride-binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation. Skin homogenates from mice treated with anti-IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, kit ligand (Kitl) and Tgfa; and increased mRNA expression of Tgfb1, Mmp12 and tenascin C (Tnc). In order to further decrease the accumulation of eosinophils, Sharpincpdm mice were crossed with IL5 null mice. Il5-/-, Sharpincpdm/Sharpincpdm mice had a 98{\%} reduction of circulating eosinophils and a 95{\%} decrease in cutaneous eosinophils compared with IL5-sufficient Sharpincpdm mice. The severity of the lesions was similar between IL5-sufficient and IL5-deficient mice. Double mutant mice had a significant decrease in Abp1, and a significant increase in Tgfb1, Mmp12 and Tnc mRNA compared with controls. These data indicate that eosinophils are not essential for the development of dermatitis in Sharpincpdm mice and suggest that eosinophils have both pro-inflammatory and anti-inflammatory roles in the skin of these mice.",
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