HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yusuf, N. Articles by Elmets, C. A. Search for Related Content PubMed PubMed Citation Articles by Yusuf, N. Articles by Elmets, C. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB 1-FLUORO-2,4-DINITROBENZENE

Heat Shock Proteins HSP27 and HSP70 Are Present in the Skin and Are Important Mediators of Allergic Contact Hypersensitivity¹

Nabiha Yusuf^2,*,, Tahseen H. Nasti^*, Chun-Ming Huang^*, Brad S. Huber^*, Tarannum Jaleel^*, Hui-Yi Lin^*,, Hui Xu^*, and Craig A. Elmets^*,

^* Department of Dermatology and Skin Diseases Research Center; Biostatistics; and Bioinformatics Unit, Division of Preventive Medicine University of Alabama at Birmingham; and Veteran Affairs Medical Center, Birmingham, AL 35294

Proteomic analysis of murine skin has shown that a variety of heat shock proteins (HSPs) are constitutively expressed in the skin. Using murine allergic contact hypersensitivity as a model, we investigated the role of two heat shock proteins, HSP27 and HSP70, in the induction of cutaneous cell-mediated immune responses. Immunohistochemical examination of skin specimens showed that HSP27 was present in the epidermis and HSP70 was present in both the epidermis and dermis. Inhibition of HSP27 and HSP70 produced a reduction in the 1-fluoro-2,4-dinitrobenzene contact hypersensitivity response and resulted in the induction of Ag-specific unresponsiveness. Treatment of dendritic cell cultures with recombinant HSP27 caused in the up-regulation of IL-1β, TNF-, IL-6, IL-12p70, and IL-12p40 but not IL-23p19, which was inhibited when Abs to HSP27 were added. The 1-fluoro-2,4-dinitrobemzene-conjugated dendritic cells that had been treated with HSP27 had an increased capacity to initiate contact hypersensitivity responses compared with control dendritic cells. This augmented capacity required TLR4 signaling because neither cytokine production by dendritic cells nor the increased induction of contact hypersensitivity responses occurred in TLR4-deficient C3H/HeJ mice. Our findings indicate that a cascade of events occurs following initial interaction of hapten with the skin that includes increased activity of HSPs, their interaction with TLR4, and, in turn, increased production of cytokines that are known to enhance Ag presentation by T cells. The results suggest that HSPs form a link between adaptive and innate immunity during the early stages of contact hypersensitivity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants P30 AR050948 (to C.A.E.) and P30 AR050948, Veterans Affairs Merit Review Award 18-103-02 (to C.A.E.), and a grant from the Department of Defense.

² Address correspondence and reprint requests to Dr. Nabiha Yusuf, Department of Dermatology; University of Alabama at Birmingham, 1670 University Boulevard, VH 566A, PO Box 202, Birmingham, AL 35294. E-mail address: nabiha{at}uab.edu

³ Abbreviations used in this paper: HSP, heat shock protein; CHS, contact hypersensitivity; DNFB, 1-fluoro-2,4-dinitrobenzene; DNBS, 2,4-dinitrobenzene sulfonic acid; DC, dendritic cell; BMDC, bone marrow-derived DC.