PMID- 19650867 OWN - NLM STAT- MEDLINE DCOM- 20100629 LR - 20211020 IS - 1600-0625 (Electronic) IS - 0906-6705 (Print) IS - 0906-6705 (Linking) VI - 19 IP - 3 DP - 2010 Mar TI - Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice. PG - 252-8 LID - 10.1111/j.1600-0625.2009.00944.x [doi] AB - Sharpin-deficient (Sharpin(cpdm)) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil-depletion in chronic inflammation, Sharpin(cpdm) 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, Sharpin(cpdm) mice were crossed with IL5 null mice. Il5(-/-), Sharpin(cpdm)/Sharpin(cpdm) mice had a 98% reduction of circulating eosinophils and a 95% decrease in cutaneous eosinophils compared with IL5-sufficient Sharpin(cpdm) 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 Sharpin(cpdm) mice and suggest that eosinophils have both pro-inflammatory and anti-inflammatory roles in the skin of these mice. FAU - Renninger, Matthew L AU - Renninger ML AD - Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA. FAU - Seymour, Rosemarie E AU - Seymour RE FAU - Whiteley, Laurence O AU - Whiteley LO FAU - Sundberg, John P AU - Sundberg JP FAU - Hogenesch, Harm AU - Hogenesch H LA - eng GR - K08 AI060707-01A1/AI/NIAID NIH HHS/United States GR - R01 AR049288/AR/NIAMS NIH HHS/United States GR - R01 AR049288-01A2/AR/NIAMS NIH HHS/United States GR - AR49288-01/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090723 PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Neutralizing) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-5) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (sharpin) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Antibodies, Monoclonal/therapeutic use MH - Antibodies, Neutralizing/therapeutic use MH - Cytokines/genetics MH - Dermatitis/blood/*immunology/pathology/*therapy MH - Eosinophilia/blood/*immunology/pathology/*therapy MH - Eosinophils/*immunology/pathology MH - Female MH - Inflammation Mediators/metabolism MH - Interleukin-5/*antagonists & inhibitors/deficiency/genetics/immunology MH - Leukocyte Count MH - Matrix Metalloproteinases/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nerve Tissue Proteins/*deficiency/genetics/immunology MH - RNA, Messenger/genetics/metabolism MH - Rats PMC - PMC2852468 MID - NIHMS168006 EDAT- 2009/08/05 09:00 MHDA- 2010/06/30 06:00 PMCR- 2011/03/01 CRDT- 2009/08/05 09:00 PHST- 2009/08/05 09:00 [entrez] PHST- 2009/08/05 09:00 [pubmed] PHST- 2010/06/30 06:00 [medline] PHST- 2011/03/01 00:00 [pmc-release] AID - EXD944 [pii] AID - 10.1111/j.1600-0625.2009.00944.x [doi] PST - ppublish SO - Exp Dermatol. 2010 Mar;19(3):252-8. doi: 10.1111/j.1600-0625.2009.00944.x. Epub 2009 Jul 23.