Macrophage Inflammatory Protein 3alpha Deficiency in Atopic Dermatitis Skin and Role in Innate Immune Response to Vaccinia Virus.
From: Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
The Journal of allergy and clinical immunology
- Publish Date: Feb 2007
- ISSN: 0091-6749
- Volume: 119
- Issue: 2
- Pages: 457-63
- Medium: Print
- Language: English
- Citation (JAMA): Kim Byung Eui, Leung Donald Y M, Streib Joanne E, et al. Macrophage Inflammatory Protein 3alpha Deficiency in Atopic Dermatitis Skin and Role in Innate Immune Response to Vaccinia Virus.. J. Allergy Clin. Immunol. Feb 2007;119:457-63
Abstract
BACKGROUND: Patients with atopic dermatitis (AD) are prone to disseminated viral skin infections and therefore are not vaccinated against smallpox because of potential complications. Macrophage inflammatory protein 3alpha (MIP-3alpha) is a C-C chemokine expressed by keratinocytes that exhibits antimicrobial activity against bacteria and fungi; however, its role in antiviral innate immunity is unknown. OBJECTIVE: Evaluate the level of MIP-3alpha in AD skin and its role in the innate immune response to vaccinia virus (VV). METHODS: Macrophage inflammatory protein 3alpha levels were evaluated using real-time RT-PCR, immunodot-blot, and immunohistochemistry. The antiviral activity of MIP-3alpha was determined using a standard viral plaque assay. RESULTS: Macrophage inflammatory protein 3alpha gene expression was significantly (P < .01) decreased in AD skin (0.21 +/- 0.05 ng MIP-3alpha/ng glyceraldehyde-3-phosphate dehydrogenase) compared with psoriasis skin (0.67 +/- 0.13). This was confirmed at the protein level using immunohistochemistry. We further demonstrate that T(H)2 cytokines downregulate MIP-3alpha expression. The importance of MIP-3alpha in the innate immune response against VV was established by first demonstrating that MIP-3alpha exhibits activity against VV. Second, VV replication was significantly increased (P < .01) in keratinocytes treated with an antibody to neutralize MIP-3alpha. CONCLUSION: The current study demonstrates that MIP-3alpha exhibits antiviral activity against VV and demonstrates the importance of MIP-3alpha in the innate immune response against VV. In addition, AD skin is deficient in MIP-3alpha, in part because of the overexpression of T(H)2 cytokines in AD skin. CLINICAL IMPLICATIONS: MIP-3alpha deficiency in AD skin contributes to patients’ increased propensity toward eczema vaccinatum. Increasing MIP-3alpha or neutralizing T(H)2 cytokines could prevent adverse reactions in patients with AD after smallpox vaccination.
Mesh Headings (Keywords): Adult, Cells, Cultured, Chemokine CCL20, Chemokines, CC, Dermatitis, Atopic, Humans, Immunity, Natural, Macrophage Inflammatory Proteins, Middle Aged, Psoriasis, Skin, Vaccinia virus
Check for Full Text / PubMed Unique Identifier (PMID): 17141855
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.